chapter13 Protein Synthesis and modification
第十三章蛋白质的生物合成(共91张PPT)
密码的通用性进一步证明各种生物进化自同一祖 先。
4. 方向性（direction）：
• 指阅读mRNA模板上的三联体密码时， 只能沿5’→3’方向进行。
5. 摆动性（wobble）：
转运氨基酸的tRNA的反密码需要通过碱基互补与 mRNA上的遗传密码反平行配对结合，但反密码与 密码之间常常不严格遵守碱基配对规律，称为摆
阶段。
一、多肽链合成的起始阶段
（一）原核生物翻译起始复合物形成
• 包括以下几个步骤：
➢核蛋白体大小亚基分离；
➢mRNA在小亚基定位结合；
➢起始氨基酰-tRNA的结合；
➢核蛋白体大亚基结合。
1. 核蛋白体大、小亚基分离： IF-1和IF-3与小亚基结合，促进核蛋白体大、小亚
基拆离，为新一轮合成作准备。
• 成肽是由转肽酶（transpeptidase）催化的 肽键形成过程。
• 在转肽酶的催化下，将P位上的tRNA所携带 的甲酰蛋氨酰基或肽酰基转移到A位上的氨 基酰tRNA上，与其-氨基缩合形成肽键。
• 此步骤需Mg2+，K+。
成肽反应过程
3. 转位（translocation）：
• 延长因子EF-G有转位酶（translocase）活性，可 促进核蛋白体向mRNA的3´侧移动相当于一个密码 的距离，同时使肽酰基tRNA从A位移到P位。
氨基酰tRNA合成酶催化的反应
第一步：活化反应
氨基酸 ＋ATP-E → 氨基酰-AMP-E ＋ PPi
第二步：连接反应
氨基酰-AMP-E ＋
tRNA
↓
氨基酰-tRNA ＋
有高度特 异性。
白细胞介素13刺激成纤维细胞胶原基因转录和胶原蛋白的合成_熊丽霞
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Ｂａ ｓ ｉｃ
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Ｊ ｉａ ｎｇｘｉ Ｐ ｒｏｖｉｎｃｉａ ｌ
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８１＊
Ｒｅ ｃｅ ｉｖｅ ｄ： ２００７－０３－０１ Ａｃｃｅ ｐｔｅ ｄ： ２００７－０４－０６
Ｘｉｏｎｇ ＬＸ， Ｓ ｈｉ ＸＹ， Ｌｉ ＷＬ， Ｚｈｏｕ Ｙ， Ｔａｎｇ ＨＬ．Ｉｎｔｅｒｌｅｕｋｉｎ－１３ ｓ ｔｉｍｕｌａｔｅｓ ｔｈｅ ｔｒａｎｓ ｃｒｉｐｔｉｏｎ ｏｆ ｃｏｌｌａｇｅｎ ｇｅｎｅ ａｎｄ ｔｈｅ ｓ ｙｎｔｈｅｓ ｉｓ ｏｆ ｃｏｌｌａｇｅｎ ｐｒｏｔｅｉｎ ｉｎ ｆｉｂｒｏｂｌａｓ ｔｓ ．Ｚｈｏｎｇｇｕｏ Ｚｕｚｈｉ Ｇｏｎｇｃｈｅｎｇ Ｙａｎｊｉｕ ｙｕ Ｌｉｎｃｈｕａｎｇ Ｋａｎｇｆｕ ２００７；１１（２３）：４４６６－４４６９（Ｃｈｉｎａ） ［ｗｗｗ．ｚｇｌｃｋｆ．ｃｏｍ／ｚｇｌｃｋｆ／ｅｊｏｕｒｎａｌ／ｕｐｆｉｌｅｓ ／０７－２３／２３ｋ－ｓｔｉｍｕｌａｔｅｓ ｔｈｅ ｔｒ ａｎｓｃｒ ｉｐｔｉｏｎ ｏｆ ｃｏｌｌａｇｅｎ ｇｅｎｅ ａｎｄ ｔｈｅ ｓｙｎｔｈｅｓｉｓ ｏｆ ｃｏｌｌａｇｅｎ ｐｒ ｏｔｅｉｎ ｉｎ ｆｉｂｒ ｏｂｌａｓｔｓ
国际商务 查尔斯希尔IM_Chapter_13
The Organization of International Business∙ Identify the different kinds oforganizational structures andinternal control mechanismsthat international businessescan use to manage globaloperations.∙ Discuss the advantages anddisadvantages of centralizedand decentralized decisionsystems.∙ Present the basic types oforganizational forms thatmultinational firms use.∙ Describe the control systemsand integrating mechanismsavailable to multinational firms∙ Show how the organizationalarchitecture, control systems,integrating systems, anddecision making choicesmultinational firms haveavailable must be consistentwith their strategy and industryenvironmentThis chapter identifies the organizational architecture that international businesses use to manage and direct global operations. The core argument outlined in this chapter is that superior enterprise profitability requires three conditions: First, the different elements of a firm’s organizational architecture must be internally consistent. Second, the organizational architecture must match or fit the strategy of the firm —strategy and architecture must be consistent. Third, the strategy and architecture of the firm must be consistent with competitive conditions prevailing in the firm’s markets. 13OUTLINE OF CHAPTER 13: THE ORGANIZATION OF INTERNATIONAL BUSINESSOpening Case: A Decade of Organizational Change at UnileverIntroductionOrganizational ArchitectureOrganizational StructureVertical Differentiation: Centralization and DecentralizationHorizontal Differentiation: The Design of StructureIntegrating MechanismsControl Systems and IncentivesTypes of Control SystemsIncentive SystemsControl Systems, Incentives, and Strategy in the International Business ProcessesOrganizational CultureCreating and Maintaining Organizational CultureOrganizational Culture and Performance in the International Business Synthesis: Strategy and ArchitectureLocalization StrategyInternational StrategyGlobal Standardization StrategyTransnational StrategyEnvironment, Strategy, Architecture, and PerformanceOrganizational ChangeOrganizational InertiaImplementing Organizational ChangeChapter SummaryCritical Thinking and Discussion QuestionsClosing Case: Strategic and Organizational Change at Black & DeckerTEACHING SUGGESTIONSIn order to get students thinking about the trade-off implicit in any strategic choice, this small group or individual exercise can be used at the beginning of class.You’ve developed very popular up-scale but reasonably priced clothing fashion line for young people, producing designs in a number of countries, manufacturing in low-cost locations, and with retail outlets in major US and European cities. Demand is popping and you have access to plenty of production capacity and capital. How should you organize the business outside the U.S.? Should you set up reasonably independent companies, subsidiaries, in each foreign market? What would that do and not do for you? Or do you want to impose a strict brand image, procedures, and central planning from headquarters, where your offices are? What are the plusses and minuses of that approach? TRANSITIONThe connection with the Unilever Opening Case is clear. They began with a decentralized system and have been rapidly moving towards increasing integration.∙Unilever is a $50 billion company selling more than 1000 products in virtually every country.∙Historically Unilever was organized into decentralized subsidiaries in each major national market. In the early 1990s there were 17 Unilever subsidiariesin Europe.∙Decentralization allowed local managers to respond to its unique market conditions and was a source of strength.∙Unilever worked hard to build a common culture to knit together a decentralized disparate organization.∙By the mid 1990s Unilever’s decentralized structure was working against its efforts to build global brands and cut costs in the face of competition.∙In 1996 Unilever introduced a new structure based on regional business groups.∙The 17 European companies relinquished autonomy in their markets to help develop a unified pan-European strategy.LECTURE OUTLINE FOR CHAPTER 13This teaching outline follows the PowerPoint presentation provided along with this instructor’s manual. The PPT slides include extensive notes that are printable under view—notes page. What follows is a summary.Slide 13-3 Opening Case: Organizational Change at UnileverWhen its structure was decentralized, Unilever used meetings and conference to create a common culture. However, there was still a lot of waste related to redundancy in the organization. The 1996 reorganization by regional business groups and the use of programs such as Lever Europe developed new capabilities in cost reduction as well as global product introduction.Slide 13-4 IntroductionOrganization architecture includes structure, control systems, incentives, processes, culture and people. Three consistency conditions must be satisfied for an organization to deliver profitability: architecture must be internally consistent; strategy and architecture must be consistent; strategy and architecture together must be consistent with the competitive environment of the firm.Slides 13-5, 13-6, 13-7 Organizational ArchitectureStructure and control systems establish decision-making responsibilities and integration mechanisms. Control systems measure and evaluate managerial performance and the performance of sub-units. Incentives connect to control systems, and processes need to be consistent with the strategic objectives of the organization. Efforts to shape values and norms in an organization are intricately linked to human resource practices, especially at the selection and recruitment stages.Slide 13-8 Organizational StructureVertical differentiation locates descision-making. Horizontal differentiation locates control boundaries (units/sub-units). Integrating mechanisms provide for coordination. Slide 13- 9 Centralization v. DecentralizationThe trade-offs here are control and local responsiveness.Slide 13-10 Horizontal Differentiation (HD)The typical entrepreneurial firm begins with no formal structure. As the firm grows, when the decision load becomes too intense for one person to handle, the firm is split into functions representing value creation activities. If growth continues, eventually the complexities of size push for the re-structuring of the firm into a divisional form.Slide 13-11 Typical Functional StructureSlide 13-12, 13-13 International DivisionThe International Division structure is organized by geography.Slide 13-14 Problems with the International StructureThese have to do with conflict between foreign and domestic, foreign managers given a secondary role, and lack of coordination.Slide 13-15 International Structural Stages ModelSlides 13-16, 13-17 Worldwide Area StructureThe world is divided into areas. An area may be a country or a group of countries. Each area is self-contained and autonomous. While this structure supports local responsiveness, it can lead to fragmentation because of lack of coordination across the areas.Slides 13-18, 13-19 Worldwide Product Divisional StructureSome firms shift to a worldwide product divisional structure as international growth increases. Each product division is autonomous and responsible for its own value creation activities. This gives managers latitude to realize location and experience curve economies. However, area or country managers tend to have little voice in this structure and this can have a devastating effect on local responsiveness.Slides 13-20, 13-21 Global Matrix StructureWhen a firm’s strategy simultaneously demands location and experience curve economies, local responsiveness, and internal transfer of core competencies the global matrix structure does the best job. It is an attempt to simultaneously capture the benefits of the worldwide area structure and the worldwide product divisional structure. The balancing act of the global matrix structure comes with its own challenges. It slows down decision making, increases the likelihood of conflict between the area structure and the product structure, and accountability is always a challenge when each manager has to wear 2 hats – one area-specific and one product-specific.Slide 13-22 Integrating MechanismsDifferent strategies make different demands on the manager in terms of the need for coordination.Slide 13-23 Impediments to CoordinationDiffering goals and lack of respect; different orientations due to different tasks; differences in nationality, time zone and distance.Slides 13-24, 13-25 Formal Integrating SystemsDirect contact, liaison roles, teams, and matrix structuresSlides 13-26, 13-27 Informal Integrating MechanismsInformal integration is a way around problems with the formal systems. It requires the organization have a teamwork spirit that embraces as many managers as possible in order to make informal mechanisms work. Two common techniques that are used to establish informal networks are; (1) the use of an appropriately designed information system (2) the use of management development policies that promote network behavior.Slide 13-28 Control systems and incentivesSlide 13-29 Factors that Influence Incentive Systems(1) The seniority of the employee and the nature of work done (2) The output target set for the employee and the degree of influence (3) The amount of cooperation between subunit managers (4) National differences in institutions and culture.Slides 13-30, 13-31 Performance AmbiguityPerformance ambiguity exists when the causes of a subunit’s poor performance are not clear and it is caused by the high degree of interdependence between subunits within the organization.Slide 13-32 Implications for Control and IncentivesThe costs of controlling transnational firms are higher than the costs of controlling firms pursuing other strategies.Slide 13-33 ProcessesIn a global enterprise many processes pose severe challenges to managers because they cut across organizational boundaries as well as national boundaries (e. g: product development). Also, valuable new processes that could create significant competitive advantage could develop anywhere in the firm’s global network.Slide 13-34Organizational CultureOrganizational culture is a social construct, a system of values and norms shared among people.Slide 13-35 Culture and PerformanceStrong cultures and adaptive cultures. The ―correct‖ culture is context-specific.Slide 13-36 Synthesis of strategy and ArchitectureSlide 13-37, 13-38 Organizational ChangeChange is often difficult to achieve due to organizational inertia. The inertia may arise from several sources: possible redistribution of power and influence among managers; strong existing cultur e; senior manager’s preconceptions about the appropriate business model; institutional constraints such as national regulations including local content rules regarding layoffs. Unfreeze-move to new state-refreeze.Slide 13-39 Looking Ahead to Chapter 14Entry Strategy and Strategic AlliancesANSWERS TO CRITICAL THINKING AND DISCUSSION QUESTIONS FOR CHAPTER 13QUESTION 1: "The choice of strategy for a multinational firm to pursue must depend upon a comparison of the benefits of that strategy (in terms of value creation) with the costs of implementing that strategy (as defined by organizational architecture necessary for implementation). On this basis, it may be logical for some firms to pursue a multi domestic strategy, others a global or international strategy, and still others a transnational strategy." Is this statement correct?ANSWER 1: Yes, this statement is correct. There is a cost-benefit trade-off with strategy choice. The costs of structure and controls for different strategies can differ widely. Transnational is usually very high, while localization is quite low. On the other hand, a localization strategy does not confer the many benefits of international, global, or transnational strategies. Remember that the strategy must fit with the competitive environment of the firm and the organizational structure and control systems of the firm must be consistent with its strategy. (See Table 13.2)QUESTION 2: Discuss this statement. "An understanding of the causes and consequences of performance ambiguity is central to the issue of organizational design in multinational firms."ANSWER 2: Organizational design creates interdependence, which may lead to performance ambiguities. Different organizational designs can remove performance ambiguities, shift them to a different level in the hierarchy, or create new performance ambiguities. It makes sense to analyze the cause of performance ambiguities as a part of the organizational design process. It also makes sense to analyze the opportunities for performance ambiguity that a new design might present. How an international company is organized (its architecture) may be a main reason a company does or does not perform well.QUESTION 3: Describe what organizational architecture a transnational firm might adopt to reduce the costs of control.ANSWER 3: A transnational, like all multinational firms, can use bureaucratic and output controls to some extent. However, the use of output controls is limited due to performance ambiguities. Bureaucratic controls are less effective when there are multiple lines of responsibility. Incentives for cooperation are one way to address this challenging issue. Another is the development of a strong culture. This culture could encourage cooperation by encouraging managers to buy into norms and value systems related to high performance. Such a culture could also give managers from interdependent sub-units an incentive to look for ways to work out any problems that might arise between them. A strong, success-oriented culture would lead to lower control costs.QUESTION 4: What is the most appropriate organizational architecture for a firm that is competing in an industry where a global strategy is appropriate?ANSWER 4: When a global strategy is appropriate, a company believes that its market is the world, and that it seeks economies of scale through the development and manufacture of a standardized product. An appropriate organizational architecture would be moderate decentralization with worldwide product divisions. There needs to be a lot of coordination, many integrating mechanisms, and a strong culture. Examples of companies pursuing global strategies are Intel, Motorola, and Texas Instruments.QUESTION 5: If a firm is changing its strategy from an international to a transnational strategy, what are the most important challenges it is likely to face in implementing this change? How can the firm overcome these challenges?ANSWER 5: The most important challenges are likely to be related to control, as the firm moves from at least a partial reliance on output measures and bureaucratic methods to one that will require many formal and informal controls and integration mechanisms. Significant performance ambiguities may occur with transnational strategies. A way to address these challenges is with a very strong culture and many integrating mechanisms. Examples of companies addressing the complex challenges of a transnational strategy are Ford, GM, Caterpillar, and ABB.CASE DISCUSSION QUESTIONSQUESTION 1: How would you characterize Black & Decker’s international expansion during the 1950s and 1960s? What strategy was the company pursuing? What was the key feature of the international organization structure that Black & Decker operated with at this time? Did Black & Decker’s strategy and structure make sense given the competitive environment at that time?ANSWER 1:Black & Decker’s early international expansion was localized, marked by great independence and decentralization. ―. . .All business functions (marketing, engineering, manufacturing, etc) are kept as close as possible to the market to be served‖—from the 1979 Annual Report. This strategy made sense at the time because there was little competition.QUESTION 2: How did the competitive environment confronting Black & Decker change during the 1980s and 1990s? What changes did Black & Decker make in its (a) strategy and (b) structure to compete more effectively in this new environment? ANSWER 2: In the 1980s and 1990s, competition increased. Bosch, Makita and Panasonic had entered the power tools game. Black & Decker’s former monopoly position in the sector now faced serious threat. To confront this threat, Black & Decker sought economies by closing factories, centralizing R&D, centralizing production decisions while keeping efficient local factories up and running, and rationalizing the workforce. This is an international strategy phase. The structural change was from a series of relatively independent subsidiaries to a more centralized organization. QUESTION 3: By the 2000s what strategy was Black & Decker pursuing in the global market place? How would you characterize its structure? Did the structure fit the strategy and environment?ANSWER 3: By 2002, Black & Decker moved their production to low cost global centers in China, Mexico and the Czech Republic, and did all their R&D and new product development work in two centers in the U.K. and U.S. Black & Decker has moved on to a global strategy phase, with production in low cost locations and R&D in areas that havea comparative advantage for that work. That means headquarters is making many decisions and there is little localization.QUESTION 4: Why do you think it took the best part of two decades for Black and Decker to effect a change in strategy and structure?ANSWER 4: The strategy seems to have evolved with changing competitive conditions. It must be quite difficult to be successful, own the market, as Black & Decker did in the 1980ies, and at the same time, figure out how to adapt to what has not yet happened, but what was inevitable: that competition would see their huge market and want a piece of it. Also, effecting structural and strategic change can be difficult and take a long time. globalEDGE™ Exercise Questions/U se the globalEDGE™ site to complete the following exercises:Exercise 1The Financial Times newspaper and the auditing firm PricewaterhouseCoopers conduct an annual survey and publish the rankings of World’s Most Respected Companies. PricewaterhouseCoopers provides the whole report downloadable as a PDF file. Locate the most recent ranking available and focus on the introductory analysis. Prepare an executive summary of the strategic and organizational success factors that make a company "most respected".Exercise 2The globalEDGE™ presents selected articles from the business print media under its Knowledge Room section. Locate the Selected Articles section and find an article that provides insights about the four key challenges facing firms in the globalization process. Prepare a description of these challenges and the solutions that the authors recommend. ANSWERS FOR globalEDGE EXERCISESChapter 13 – Exercise 1The World’s Most Respected Companies rankings can be located by searching for the name of the ranking at /ibrd/ibrd.asp. The resource is titled―Financial Times:World’s Most Respected Companies‖ and is located under the globalEDGE™ Category ―Research: Rankings‖. The rankings from are only available through subscription, but PricewaterhouseCoopers provides access to the results through a PDF download.Search Phrase: ―World’s Most Respected Companies‖Resource Name: Financial Times:World’s Most Respected CompaniesWebsite:/Extweb/ncsurvres.nsf/docid/D2345E01A80AC14885256CB0 0033DC8FglobalEDGE™ Category: ―Research: Rankings‖Chapter 13 – Exercise 2The selected articles section can be accessed via the ―knowledge room‖ web page at /KnowledgeRoom/KnowledgeRoom.asp. Also, the full list of the articles is located under the selected articles webpage at/KnowledgeRoom/SelectedArticles/index.asp. ―Th e Changing Face of Global Business‖ is an article published by the Optimize Magazine and can be reached at/article/showArticle.jhtml?articleId=21400849&pgno=1. Location: Knowledge Room / Selected ArticlesResource Name: The Changing Face of Global BusinessWebsite:/article/showArticle.jhtml?articleId=21400849&pgno=1 globalEDGE™ Category: ―Selected Articles‖SUGGESTED VIDEO NOTETitle 14: General Motors/SaabSummaryGM, the world’s largest automaker, is changing the way it does business. Despite profitability issues, the company has increased its R&D budget demonstrating its commitment to innovation. GM believes the way of the future requires the company to leverage its global engineering resources, relationships, skills, and knowledge. The company hopes that this global approach will eventually pay off in the form of higher profits. To that end, GM has established the Global Research Network designed to bring together technical expertise from around the world, and in the process, eliminate the traditional more isolated approach to innovation.GM’s new business model has required the company to make some substantial changesto the way its R&D division operates. The company is emphasizing collaboration between and among researchers, universities, national laboratories, suppliers, and even other auto manufacturers. To achieve its goal, GM is promoting physical meetings between researchers, e-mailing, net meeting, and so on. GM has also established a science center in Sweden that is situated such that not only are the technical people and manufacturing people physically very close, but they also have easy access to universities. This video relates to the material on strategic alliances in Chapter 14, the discussion of organizational culture in Chapter 13, the notion of strategy in Chapter 12, and material on R&D in Chapter 17.International Business: Competing in the Global Marketplace Sixth Edition Chapter 13 Discussion Questions1. GM is promoting a substantial shift in its corporate culture in the area of research, going from the traditional lone wolf mentality to a highly collaborative model. How can the company ensure the transformation occurs? What can the company do to facilitate the process?2. The SAAB brand is at the center of GM’s new business model. Will the model successfully extend to its other products? Why or why not?3. GM is promoting collaboration between its own researchers and researchers at other firms including the competition and the company’s suppliers. How can the company protect itself from opportunistic behavior from its research partners?4. GM has recently opened a new science office in Sweden. The company hopes that the center will benefit not only the SAAB brand, but the entire GM product line. Consider the center, its layout, how it came into existence, and so on. Can this type of center exist elsewhere in the GM network? Why or why not?199。
Chapter 13 PRICING, QUOTATIONS, AND TERMS
An important aspect of your company’s pricing analysis is the determination of market objectives. For example, you may ask whether your company is attempting to penetrate a new market, seeking long-term market growth, or looking for an outlet for surplus production or outmoded products.
Other costs should be assessed for domestic and export products according to how much benefit each product receives from such expenditures. Additional costs often associated with export sales include the following: • Fees for market research and credit checks • Business travel expenses • International postage and telephone rates • Translation costs • Commissions, training charges, and other costs involving foreign representatives
Costs
The computation of the actual cost of producing a product and bringing it to market is the core element in determining if exporting is financially viable. Many new exporters calculate their export price by the cost-plus method. In that calculation, the exporter starts with the domestic manufacturing cost and adds administration, research and development, overhead, freight forwarding, distributor margins, customs charges, and profit.
生物化学 Protein Biosynthesis(93-4)
proteins （50）
3. 核糖体结构模型 大亚基：氨酰基位点（A），肽酰基位点（P） 大小亚基触面上有一个mRNA结合位点。
4. 多核糖体 在一个 mRNA 上有多个核糖体，它们能分
别合成一条完整的肽链。
可提高蛋白质合成的效率。
Polyribosomes
二、tRNA和氨酰基-tRNA 60-120种tRNA，20种氨酰-tRNA合成酶。 tRNA的功能：氨基酸活化；识别密码子 一种氨基酸能够接到多种tRNA上，这些 运载同一种氨基酸的tRNA互为同工tRNA。
第五节 蛋白质运输和定位
新合成的多肽定向输送和定位。 原核蛋白质在胞质中合成后，一部分留
在胞质中，另一部分被运送到质膜、外膜
和胞外。 真核蛋白质主要在胞质中合成，一部分 留在胞质中，其余送往各个细胞器或胞外。
真核细胞蛋
白质的运输
一、蛋白质的信号肽与跨膜转运
1. 信号肽（signal sequence） 带有蛋白质去向信息的一段序列，通
二、链霉素、新霉素、卡那霉素
氨基环醇类抗生素。 与30S亚基结合，阻止起始复合物的形成。 还可改变核糖体构象，引起翻译错误。
链霉素
三、四环素、土霉素、金霉素
四环素族抗生素。 结合原核30S亚基，封闭其的A位点， 使得氨酰-tRNA无法进入与mRNA结合，
阻断肽链延伸。
四环素
四、氯霉素
结合原核50S亚基，抑制肽基转移酶活性。 也可抑制真核生物线粒体内蛋白质的合成。
真核CBP帽结合蛋白 （cap-binding protein）
CBPⅠ和IF4F与mRNA的5’端帽子结合。
三、mRNA的结构与翻译 1. 原核多顺反子mRNA的翻译 各个顺反子间隔1-100个核苷酸。 乳糖操纵子 Z基因：半乳糖苷酶 产物相对量 1.0
Protein Synthesis
tRNA Tertiary Structure (L-shaped)
• RNA tertiary structure depends on interactions of bases at distant sites.
IF2 has a ribosome-dependent GTPase activity. Energy is needed to form an active ribosome.
Protein Synthesis Occurs by Initiation, Elongation, and Termination
• Protein synthesis falls into the three stages: Initiation, Elongation, Termination.
code for 20 amino acids • Universal
Further reading: Chapter 9: Using the Genetic Code, Gene IX
证实三联子组成一密码子
• 研究烟草坏死卫星病毒发现 ，其外壳蛋白亚基由400个 氨基酸组成，相应的RNA片 段长1200个核苷酸，与密码 三联子体系正好相吻合。
• Ribosome (rRNA & ribosomal proteins): the translation apparatus with catalyzing activity
Using the Genetic Code
市场营销英文版Chapter-13Marketing-Channels-and-Supply-Chain-Management
13 - 17
How a Distributor Reduces the Number of Channel Transactions
1 2 3 4 5 6 7 8 9
= Manufacturer
13 - 18
A. Number of contacts without a distributor MxC=3X3=9
13 - 2
Case Study
Caterpillar
Dominates world’s markets for heavy construction and mining equipment. Independent dealers are key to success Dealer network is linked via computers
13 - 1
Objectives
Comprehend how companies select, motivate, and evaluate channel members. Understand the nature and importance of marketing logistics and integrated supply chain management.
Factory
Ship
• Produce to forecast
Supplier
Ship
• Produce to forecast • Produce to order with lead time
13 - 8
What is a Supply Chain?
P&G or other manufacturer Jewel or third party Jewel Supermarket Customer wants detergent and goes to Jewel
基础分子生物学课件
6.6 Use of fMet-tRNAf is controlled by IF-2 and the ribosome . fMet-tRNAf的使用受IF-2因子和 核糖体所调节.
• IF-2结合起始子fMet-tRNAf, 使其进入 30S亚基的局部P位.
基础分子生物学课件
只有fMet-tRNAf 才能被30S亚基 用于起始; 只有 其他的氨酰tRNA (aa-tRNA) 才能被70S核糖 体用于延伸.
Chapter 6
Protein synthesis 蛋白质合成
基础分子生物学课件
6.1 Introduction 引言
尺寸比较 显示核糖 体足以结 合tRNA和 mRNA.
基础分子生物学课件
核糖体是一个大 的核糖核蛋白颗 粒, 它含有较多的 RNA和较少的蛋 白质, 可解离成大, 小两个亚基.
基础分子生物学课件
丙肝病毒的 IRES可以直接 结合40S亚基.
基础分子生物学课件
6.9 Eukaryotes use a complex of many initiation factors 真核生物使用由多种起始因子促成的复 合体.
• 起始因子为启动的各个阶段所需, 包括结合tRNA 起始子, 40S亚基在mRNA的附着, 沿着mRNA上滑 动以及60S亚基的加入.
基础分子生物学课件
6.5 A special initiator tRNA starts the polypeptide chain. 一种特定的tRNA起始子启动肽链合成.
• 蛋白质合成通常始于AUG编码的甲硫氨酸. • 起始和延伸涉及不同的甲硫氨酰- tRNA. • tRNA起始子有独特的结构特征, 使之与其他
基础分子生物学课件
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表 14--5 每种合成酶通过几个特殊碱基来识别其同质 tRNA tRNA 一类氨基酰 tRNA 合成酶 Val Met Ile Gln 二类氨基酰 tRNA 合成酶 Phe（酵母） Ser Ala 反密码子上的三个碱基，G20(D 环); A73(末端) G1-C72; G2-C71; A3-U70(受体臂); C11-G24(D 环) G3-U70(受体臂) 反密码子上的三个碱基 反密码子上的三个碱基 反密码子上的 C34 修饰碱基 U35（反密码子）; U1-A72 和 G73（受体臂） 合成酶识别的碱基
A G
A G U A G C CCUGCGGUU ACCUCCUUUA3 ’ G 3 ’ GGAGGA G G A 5’ mRNA
U
G
C
C
A
A
U
G
G
A
5’ 图 15- 16S rRNA 和 S-D 序列互补配对
原核生物翻译起始因子
表 15-2 E.coli 蛋白质合成起始所需的三种起始因子 因子 IF3 IF2 IF1 质 量 （KDa） 23 97.3 9 因子/ 核 糖体 25% ? 15% 功能 亚基解离与 mRNA 的结合 起始 tRNA 的结合与 GTP 水解 循环因子？
活性位点 mRNA 结合 位点 P 位点 A 位点
E 位点 5SRNA 肽酰基转移 酶 EF-Tu 结 合 位点 EF-G 结 合 位点 L7/L12
表 14-8 核糖体的活性位点 功能 位置 组分 结合 mRNA 和 IF 30S,P 位点附近 S1、S18、S21；及 S3、S4、S5、 因子 S12 16SrRNA3′末端区域 结合 fMet-tRNA 和 大部分在 50S 亚基 L2、L27 及 L14、L18、L24、L33 肽基-tRNA 16S 和 23SrRNA3′附近区域 结合氨酰基-tRNA 大部分在 30S 亚基 L1、L5、L7/L12、L20、L30、L33 16S 和 23SrRNA（16S 的 1400 区） 结合脱酰 tRNA 50S 23SrRNA 是重要的 和 23SrRNA 结合 P 和 A 位点的附近 L5、L18、L25 复合体 将肽链转移到氨基 50S 的中心突起 L2、L3、L4、L15、L16 23SrRNA 酰-tRNA 上 是重要的 氨基酰 -tRNA 的进 30S 外部 入 移位 50S 亚 基 的 界 面 上，L7/L12 附近， 近 S12 GTP 酶需要 50S 的柄 L7、L12
NH2 RCH CO AMP 正确 tRNA 结合快 解离慢 NH2 RCH CO AMP AMP RCH CO NH2 不正确 tRNA 结合慢 解离快
正确 tRNA 触发 酶构 象改变
NH2 RCH CO AMP
迅速产生 氨酰tRNA
NH2 RCH CO
NH2 RCH CO
酶的构象未 发生改变 氨酰化进行 缓慢
Aminoacyl-tRNA synthetase 氨酰tRNA合成酶 (aaRS)
• I类与tRNA受体茎和反密码子茎的小沟结合， N端含有ATP结合结构域，C端含有反密码 子臂结合结构域，先将氨基酸转移到tRAN 的2’-OH上，而后切换到3’-OH。Arg, Cys,Gln,Glu,Ile,Leu,Met,Trp,Tyr,Val • II类aaRS以N端结构域与受体茎和反密码子 茎的大沟结合，C端结合ATP，将氨基酸结 合到3’-OH上(苯丙氨酸除外)。 Ala,Asn,Asp,Gly,His,Lys,Phe,Pro,Ser,Thr
甲酰甲硫氨酰fMet-tRNAfMet
图9-7 tRNAAla的一级结构、二级结构和三级结构
图9-8 E. coli起始tRNA的结构
tRNA的结构和功能
tRNA的结构 （一）三叶草型的二维结构 • (1)各种tRNA均含有70~80个碱基，其 中22个碱 基是恒定的。 • (2) 5’端和3’端配对（常为7bp）形成茎区，称为 受体臂（acceptor arm）或称氨基酸臂 。在3’端 永远是 4个碱基（XCCA）的单链区，在其末端 有 2’-OH 或 3’-OH ，是被氨基酰化位点。此臂负 责携带特异的氨基酸。
• （3）TψC常由5bp的茎和7Nt和环组成。此 臂负责和核糖体上的rRNA 识别结合； • (4)反密码子臂(anticodon arm)常由5bp的 茎区和7Nt的环区组成，它负责对密码子的 识别与配对。 • (5)D环 (D arm)的茎区长度常为4bp，也称 双氢尿嘧啶环。负责和氨基酰tRNA聚合酶 结合; • (6)额外环(extra arm)可变性大，从4 Nt到 21 Nt不等，其功能是在tRNA的L型三维结 构中负责连接两个区域（D环－反密码子环 和TψC-受体臂）。
分子生物学系列讲座之6
Welcome to molecular biology class
13 Protein Synthesis and modification 蛋白质的合成与修饰
Department of Life science
Key terms
密码子(codon) ，反密码子(anticodon) 密码子的摆动性(wobbling) ，密码子的简 并性(degeneracy) ，同义密码子 (synonymous codon) 同工受体-tRNA (isoacceptor tRNA) 多聚核糖体(polyribosome) SD序列(SD sequence ) ，反SD序列 信号肽(signal peptide)
图 15－5 氨基酰合成酶的动力学校正
NH2 RCH CO AMP
腺苷化
NH2 RCH CO AMP
结合tRNA
校对：氨基酰－腺苷被水解
NH2 RCH CO AMP 负载tRNA
错误的 氨基酸 AMP
NH2 RCH COOH
校对：氨基酰－tRNA被水解 NH2 RCH CO 错误的 氨基酸 AMP NH2 RCH COOH
二. tRNA对氨基酸的识别
• （1） tRNA怎样接受特定的氨基酸， 氨基酰 －tRNA合成酶怎样识别tRNA； • （2） tRNA中的哪些结构和接受特定氨 基酸有关。
• 1988 年 Hou Ya-ming （候雅明）和 Schimmel 首 先取得突破。
他们采用的方法是： • (1) 选用E.coli (trp-)来进行研究； • (2) tRNA，携带Ala，反密码子突变成CUA，可以 和终止密码子UAG相配对,可校正色氨酸的琥 珀突变. • (3) 用点突变的方法来改变校正tRNA（Ala）上各 个位点，观察对识别Ala有何影响，他们证明 了 Ala tRNA的G3:U70碱基对，仅一对碱基决定了 丙氨酰tRNA合成酶与tRNA的识别。 • 这种小元件称为tRNA的“ identity”，或称为副密 码子（paracodon）。
功能 增加IF-2,3的活性
IF-2
使Met-tRNAfMet选择性地与30s亚基结合,需GTP
与30s亚基结合,使30s与mRNA起始部位连接 螺旋酶活性,使核糖体亚基保持解离状态
起始因子
IF-3а IF-3β
EF-Tu
按30s编码序列携带肽链tRNA进入A位
使EF-Tu,GTP再生,参与肽链延伸 使肽链-tRNA从A位点转移到P位点 识别终止密码子UAA,UAG
延伸因子
EF-Ts EF-G RE-1
பைடு நூலகம்
释放因子
RE-2
RE-3
识别终止密码子UAA,UGA
增强RF-1,RE-2活性
2. 起始复合物的形成
(1) IF-3和核糖体30S rRNA结合 使16S RNA和mRNA的S-D顺序结合 a.使30S 保持游离 b.形成起始复合体 I (2) IF-2 + GTP + 氨酰甲硫氨酸→中间复合体。 (3) IF-1置换出 IF-3, 50S亚基可和30S亚基结合。 (4) 50S+30S →复合体III，释放IF-1,IF-2。
• • 1. 2. 3. • • 起始: initiation factor, IF 延伸: elongation factor, EF Entry 进位 Transpeptidation 转肽 Translocation 移位 终止: release factor, RF Ribosome recycling factor, RRF
图9-6 原核生物mRNA和真核生物mRNA结构的比较
Isoaccepting tRNA, 同工受体tRNA Cloverleaf 氨基酸受体茎Acceptor stem 氨基酸臂The anticodon arm 反密码子环Anticodon loop 可变环The variable loop 起始tRNAInitiator tRNA 原核生物甲酰甲硫氨酸formylmethonine， (tRNAfMet) 真核生物 甲硫氨酸(tRNAiMet) 甲硫氨酸tRNAmMet
图9-1 核糖体的结构和化学组成
图9-2 16S rRNA的二级结构和三级结构
• • • • •
氨基位点Acceptor site, A site 多肽位点Peptidal site, Psite 出口位点Exit site, E site mRNA通道mRNA channel 肽酰转移酶活性位点Peptidyl transferase site • 多肽离开通道Exit channel • 蛋白质因子结合位点Protein factor site
图9-3 核糖体的三维结构模型和主要的功能部位
图9-4 原核细胞核糖体的各种功能部位
图9-5 原核细胞多聚核糖体的结构
• • • • • •
mRNA 开放阅读框Open reading frame 非编码序列Non-coding sequence 非翻译区untranslated region 核糖体结合位点Ribosome binding site 单顺反子monocistron