免疫球蛋白的结构与功能的关系.ppt
Immunoglobulin Structure-Function Relationship免疫球蛋白的结构与功能的关系 Signalling antigen receptors on B cells-bifunctional antigen-binding secreted molecules（B 细胞表面受体和分泌的抗体）Structural conservation and infinite variability-domain structure（结构上不仅保守而且无限可变的）.The Immunoglobulin Gene Superfamily（免疫球蛋白的超家族）The immunoglobulin fold（免疫球蛋白的折叠）Framework and complementarity determining regions-hypervariable loops（框架结构和可变区）Modes of interactions with antigens（与抗原相互作用的模型）Effector mechanisms and isotype role of the Fc.（Fc 区的作用）Multimeric antibodies and multimerisation Characteristics and properties of each Ig isotype Ig receptors and their functionsImmunoglobulin Structure-Function Relationship Cell surface antigen receptor on B cells B 细胞表面受体和分泌的抗体Allows B cells to sense their antigenic environmentConnects extracellular space with intracellular signalling machinery Secreted antibody（抗体）Neutralisation（中和作用）Arming/recruiting effector cells（激活或者诱导功能细胞）Complement fixation（帮助机体对抗原的清除）Immunoglobulin Structure-Function RelationshipImmunoglobulins are Bifunctional Proteins Immunoglobulins must interact with a small number of specialised molecules-（免疫球蛋白必须与特殊分子相互作用）Fc receptors on cells（细胞表面的Fc 受体）Complement proteins（辅助蛋白）Intracellular cell signalling molecules（细胞内信号转导分子）whilst simultaneously recognising an infinite array of antigenic determinants.（同时能够识别无限抗原族）Structural conservation and a capacity for infinite variability in a single molecule is provided by a DOMAIN structure.（结构上不仅保守而且无限可变的-抗体结构域）Ig domains are derived from a single ancestral gene that has duplicated,diversified and been modified to endow an assortment of functional qualities on a common basic structure（Ig结构域源于一个原始基因，复制，多元化，修饰等）Ig domains are not restricted to immunoglobulins（Ig 结构域不仅仅局限于免疫球蛋白）.The most striking characteristic of the Ig domain is a disulphide bond-linked structure of 110 amino acids long（Ig 结构域最明显的特点是其双硫键，连接了110 个氨基酸）.Immunoglobulin domainsThe genes encoding Ig domains are not restricted to Ig genes.Although first discovered in immunoglobulins,they are found in a superfamily of related genes,particularly those encoding proteins crucial to cell-cell interactions and molecular recognition systems.IgSF molecules are found in most cell types and are present across taxonomic boundariesIg gene superfamily-IgSFAntibodies are Proteins that Recognize Specific Antigens 抗体能够特异性的识别抗原Epitopes（抗原决定簇）:Antigen Regions that Interact with AntibodiesConsequences of Antibody Binding抗体结合效应CLVLSSSSSSSSCH3CH2CH1VHFcFabF(ab)2Domains are folded,compact,protease resistant structuresDomain Structure of Immunoglobulins免疫球蛋白的结构域Pepsin cleavage sites-1 x(Fab)2&1 x FcPapain cleavage sites-2 x Fab 1 x FcLight chain Cdomainsk or lHeavy chain Cdomainsa,d,e,g,or mCH3CH3CH2CH3CH2CH1CH3CH2CH1VH1CH3CH2CH1VH1VLCH3CH2CH1VH1CLVLCH3CH2CH1VH1CLVLHingeCH3CH2CH1VH1VLCLElbowCH3CH2FbFvFvFvFbFvHingeElbowCH3CH2FbFvFlexibility andmotion of immunoglobulinsHingeFvFbFabCH3CH2CH1VH1VLCLFcElbowCarbohydrateThe Immunoglobulin FoldThe characteristic structural motif of all Ig domainsBarrel under constructionA barrel made of a sheet of staves arranged in a folded over sheetA b barrel of 7(CL)or 8(VL)polypeptide strands connected by loops and arranged to enclose a hydrophobic interiorSingle VL domainUnfolded VL region showing 8 antiparallel b-pleated sheets connected by loops.NH2COOHS SThe Immunoglobulin Fold Immunoglobulins must interact with a finite number of specialised molecules-Easily explained by a common Fc region irrespective of specificity-whilst simultaneously recognising an infinite array of antigenic determinants.In immunoglobulins,what is the structural basis for the infinite diversity needed to match the antigenic universe?Immunoglobulins are Bifunctional ProteinsAmino acid No.Variability8010060402020 40 60 80 100 120Cytochromes CVariability of amino acids in related proteinsWu&Kabat 1970Amino acid No.Variability8010060402020 40 60 80 100 120HumanIg heavychainsFR1 FR2 FR3 FR4 CDR2 CDR3 CDR1 Distinct regions of high variability and conservation led to the concept of a FRAMEWORK(FR),on which hypervariable regions were suspended.Framework and Hypervariable regionsAmino acid No.Variability8010060402020 40 60 80 100 120 Most hypervariable regions coincided with antigen contact points-the COMPLEMENTARITY DETERMINING REGIONS(CDRs)Hypervariable regionsHypervariable CDRs are locatedon loops at the end of the Fv regions
