STRUCTURE, FUNCTION AND PROPERTIES OF ANTIBODY-BINDING SITES
STRUCTURE, FUNCTION AND PROPERTIES OF ANTIBODY-BINDING SITES
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DOI：
10.1016/0022-2836(91)90617-f
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发表时间：
1991-01-05
影响因子：
5.6
通讯作者：
OLSON, AJ
中科院分区：
文献类型：
--
作者：
MIAN, IS;BRADWELL, AR;OLSON, AJ
抗体结合部位是否具有一般性质，使它们能够以不同的亲和力结合不同的抗原和结合新的抗原？在这里，我们通过检查最有利于抗原吸收和结合的残基的物理和化学特征来解决这个问题。两亲性氨基酸可以很好地耐受抗体-抗原复合体形成过程中环境从亲水到疏水的变化。如果残基很大，可以参与各种各样的范德华相互作用和静电相互作用，就可以与一系列抗原结合。具有柔性侧链的氨基酸可以产生一个结构可塑性区域，即具有在抗原周围塑造自身的能力的结合部位，以改善相互作用表面的互补性。因此，抗体可以使用一组有限的残基与一系列新的抗原结合，其中夹杂着更独特的残基，因此可以归因于更高的结合特异性。因此，单个抗体分子可以发生交叉反应，并具有结合结构相似配体的能力。通过适度结合位点的灵活性来适应抗原结构的变化，可以通过允许抗体与不同但密切相关的病原体结合而对免疫防御做出重要贡献。Tyr和Trp最容易满足这些天主教的物理化学要求，因此有望在理论上常见的结合位点。对此的实验支持来自三个来源，(1)这些氨基酸在六个结晶学确定的抗体-抗原复合体中观察到的抗原结合的高频率参与，(2)它们经常出现在根据结构和序列数据确定的抗体的假定结合区，以及(3)它们的侧链在已知的抗体结合部位和模型系统中移动的可能性。这六个结合抗原包括两个不同的小半抗原，同一大蛋白的不重叠区域和一个19个氨基酸残基的多肽。在总共85个互补决定区域位置中，只有37个位置(加3个框架)直接参与抗原相互作用。其中，轻链残基91被所有被检查的络合物利用，而轻链32、轻链96和重链33被6个中的5个利用。已知的抗体-抗原复合体中的结合部位以及游离Fab片段中的假定结合部位在存在的氨基酸类型方面表现出类似的特征。对其他氨基酸的可能作用也进行了评估。讨论了I类主要组织相容性分子结合区的潜在含义和分子的合理设计。
Do antibody combining sites possess general properties that enable them to bind different antigens with varying affinities and to bind novel antigens? Here, we address this question by examining the physical and chemical characteristics most favourable for residues involved in antigen accommodation and binding. Amphipathic amino acids could readily tolerate the change of environment from hydrophilic to hydrophobic that occurs upon antibody-antigen complex formation. Residues that are large and can participate in a wide variety of van der Waals' and electrostatic interactions would permit binding to a range of antigens. Amino acids with flexible side-chains could generate a structurally plastic region, i.e. a binding site possessing the ability to mould itself around the antigen to improve complementarity of the interacting surfaces. Hence, antibodies could bind to an array of novel antigens using a limited set of residues interspersed with more unique residues to which greater binding specificity can be attributed. An individual antibody molecule could thus be cross-reactive and have the capacity to bind structurally similar ligands. The accommodation of variations in antigenic structure by modest combining site flexibility could make an important contribution to immune defence by allowing antibody binding to distinct but closely related pathogens.Tyr and Trp most readily fulfil these catholic physicochemical requirements and thus would be expected to be common in combining sites on theoretical grounds. Experimental support for this comes from three sources, (1) the high frequency of participation by these amino acids in the antigen binding observed in six crystallographically determined antibody-antigen complexes, (2) their frequent occurrence in the putative binding regions of antibodies as determined from structural and sequence data and (3) the potential for movement of their side-chains in known antibody binding sites and model systems. The six bound antigens comprise two small different haptens, non-overlapping regions of the same large protein and a 19 amino acid residue peptide. Out of a total of 85 complementarity determining region positions, only 37 locations (plus 3 framework) are directly involved in antigen interaction. Of these, light chain residue 91 is utilized by all the complexes examined, whilst light chain 32, light chain 96 and heavy chain 33 are employed by five out of the six. The binding sites in known antibody-antigen complexes as well as the postulated combining sites in free Fab fragments show similar characteristics with regard to the types of amino acids present. The possible role of other amino acids is also assessed. Potential implications for the combining regions of class I major histocompatibility molecules and the rational design of molecules are discussed.