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Anchor Residues in Protein-Protein Interactions
Deepa Rajamani, Spencer Thiel, Sandor Vajda, Carlos J. Camacho and Susan S. Taylor
Proceedings of the National Academy of Sciences of the United States of America
Vol. 101, No. 31 (Aug. 3, 2004), pp. 11287-11292
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3372768
Page Count: 6
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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 (≥ 100 Å2). 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.
Proceedings of the National Academy of Sciences of the United States of America © 2004 National Academy of Sciences