Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

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
Stable URL: http://www.jstor.org/stable/3372768
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Anchor Residues in Protein-Protein Interactions
Preview not available

Abstract

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.

Page Thumbnails

  • Thumbnail: Page 
[11287]
    [11287]
  • Thumbnail: Page 
11288
    11288
  • Thumbnail: Page 
11289
    11289
  • Thumbnail: Page 
11290
    11290
  • Thumbnail: Page 
11291
    11291
  • Thumbnail: Page 
11292
    11292