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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A GENERAL MODEL OF INVARIANT CHAIN ASSOCIATION WITH CLASS II MAJOR HISTOCOMPATIBILITY COMPLEX PROTEINS
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A GENERAL MODEL OF INVARIANT CHAIN ASSOCIATION WITH CLASS II MAJOR HISTOCOMPATIBILITY COMPLEX PROTEINS

机译：具有II类主要组织相容性复合蛋白的链链的通用模型

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摘要

The binding of invariant chain to major histocompatibility complex (MHC) proteins is an important step in processing of MHC class II proteins and in antigen presentation. The question of how invariant chain can bind to all MHC class II proteins is central to understanding these processes. We have employed molecular modeling to predict the structure of class II-associated invariant chain peptide (CLIP)MHC protein complexes and to ask whether the predicted mode of association could be general across all MHC class II proteins. CLIP fits identically into the MHC class II alleles HLA-DR3, I-A(k), I-A(u), and I-A(d), with a consistent pattern of hydrogen bonds, contacts, and hydrophobic burial and without bad contacts. Our model predicts the burial of CLIP residues Met-91 and Met-99 in the deep P1 and P9 anchor pockets and other detailed interactions, which we have compared with available data. The predicted pattern of I-A allele-specific effects on CLIP binding is very similar to that observed experimentally by alanine-scanning mutations of CLIP, Together, these results indicate that CLIP may bind in a single, general way across products of MHC class II alleles. [References: 17]
机译：不变链与主要组织相容性复合体（MHC）蛋白的结合是II类MHC蛋白加工和抗原呈递的重要步骤。不变链如何结合所有II类MHC蛋白的问题对于理解这些过程至关重要。我们已经使用分子建模来预测II类相关的恒定链肽（CLIP）MHC蛋白复合物的结构，并询问所预测的缔合模式是否可能在所有MHC II类蛋白上通用。 CLIP完全适用于MHC II类等位基因HLA-DR3，I-A（k），I-A（u）和I-A（d），具有一致的氢键，接触和疏水性埋葬方式，并且没有不良接触。我们的模型预测了在深度P1和P9锚袋中埋藏CLIP残基Met-91和Met-99以及其他详细的相互作用，我们将其与现有数据进行了比较。 I-A等位基因特异的对CLIP结合的预测模式与通过丙氨酸扫描CLIP突变的实验观察到的模式非常相似。这些结果共同表明，CLIP可能以单一的通用方式跨MHC II类等位基因产物结合。 [参考：17]

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