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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structure and kinetics of a transient antibody binding intermediate reveal a kinetic discrimination mechanism in antigen recognition
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Structure and kinetics of a transient antibody binding intermediate reveal a kinetic discrimination mechanism in antigen recognition

机译：瞬时抗体结合中间体的结构和动力学揭示了抗原识别中的动力学判别机制

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摘要

induced fit is a predominant phenomenon in protein-ligand interactions, yet it is invariably attributed without establishing the existence, let alone the structure, of the initial, low-affinity encounter complex. We determined the crystal structure of the encounter complex on the pathway of ligand binding by IgE antibody SPE7. We show that this complex is formed by a wide range of ligands that initially bind with identical affinity. Nonspecific ligands rapidly dissociate, whereupon the antibody isomerizes to a nonbinding isomer. Specific ligand complexes, however, slowly isomerize to give a high-affinity complex. This isomerization involves backbone and side-chain rearrangements of up to 14 angstrom and the formation of specific hydrogen bonds. The postbinding conformational switch, combined with the prebinding isomerization to an energetically favorable nonbinding isomer, results in a "kinetic discrimination" mechanism that mediates selective binding, by a factor of > 10(3), between highly related ligands that initially bind with the same affinity. This model may apply to proteins that bind multiple ligands in a specific manner or other proteins that, although capable of binding many ligands, are activated by only a few.
机译：诱导的契合度是蛋白质-配体相互作用中的主要现象，但它总是归因于没有建立最初的低亲和性遭遇复合体的存在，更不用说其结构了。我们在IgE抗体SPE7的配体结合途径上确定了遇到复合物的晶体结构。我们显示该复合物由最初以相同亲和力结合的多种配体形成。非特异性配体迅速解离，于是抗体异构化为非结合异构体。但是，特定的配体配合物会缓慢异构化，从而形成高亲和力的配合物。这种异构化涉及高达14埃的主链和侧链重排以及特定氢键的形成。结合后构象转换与结合前异构化为能量上有利的非结合异构体相结合，导致“动力学歧视”机制介导在与之最初结合的高度相关的配体之间以> 10（3）的因子介导选择性结合。亲和力。该模型可能适用于以特定方式结合多个配体的蛋白质或其他虽然能够结合许多配体但仅被少数激活的蛋白质。

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