Anchor residues in protein-protein interactions
Anchor residues in protein-protein interactions
复制标题
DOI：
10.1073/pnas.0401942101
复制
发表时间：
2004-08-03
影响因子：
11.1
通讯作者：
Camacho, CJ
中科院分区：
文献类型：
--
作者：
Rajamani, D;Thiel, S;Camacho, CJ
我们表明，分子识别的机制需要一个相互作用的蛋白质，通常是较小的两个，锚在一个特定的侧链结构约束的结合沟的其他蛋白质，提供了一个空间的约束，有助于稳定一个天然的结合中间。我们确定了39蛋白质-蛋白质复合物中的锚残基，并验证，即使在没有它们的相互作用的合作伙伴，发现的锚侧链的构象类似于在绑定复合物中观察到的。这些现成的识别基序对应于表面侧链，其在形成复合物后掩埋了最大的溶剂可及表面积（大于或等于100埃（2））。这种锚的存在意味着结合途径可以避免在结合界面的核心处的动力学上昂贵的结构重排，从而允许相对平滑的识别过程。一旦锚被对接，诱导的配合过程进一步有助于形成最终的高亲和力复合物。这个后期阶段涉及柔性（溶剂暴露）侧链，其闩锁到结合口袋外围的相遇复合物。我们的研究结果表明，进化保守的锚侧链适用于实际的结构，这些残基假设之前遇到复杂的，而不仅仅是他们的基因座。蛋白质对接的影响进行了讨论。
We show that the mechanism for molecular recognition requires one of the interacting proteins, usually the smaller of the two, to anchor a specific side chain in a structurally constrained binding groove of the other protein, providing a steric constraint that helps to stabilize a native-like bound intermediate. We identify the anchor residues in 39 protein-protein complexes and verify that, even in the absence of their interacting partners, the anchor side chains are found in conformations similar to those observed in the bound complex. These ready-made recognition motifs correspond to surface side chains that bury the largest solvent-accessible surface area after forming the complex (greater than or equal to100 Angstrom(2)). The existence of such anchors implies that binding pathways can avoid kinetically costly structural rearrangements at the core of the binding interface, allowing for a relatively smooth recognition process. Once anchors are docked, an induced fit process further contributes to forming the final high-affinity complex. This later stage involves flexible (solvent-exposed) side chains that latch to the encounter complex in the periphery of the binding pocket. Our results suggest that the evolutionary conservation of anchor side chains applies to the actual structure that these residues assume before the encounter complex and not just to their loci. Implications for protein docking are also discussed.