Transition states for protein folding have native topologies despite high structural variability

Nat Struct Mol Biol. 2004 May;11(5):443-9. doi: 10.1038/nsmb765. Epub 2004 Apr 18.

Abstract

We present a structural analysis of the folding transition states of three SH3 domains. Our results reveal that the secondary structure is not yet fully formed at this stage of folding and that the solvent is only partially excluded from the interior of the protein. Comparison of the members of the transition state ensemble with a database of native folds shows that, despite substantial local variability, the transition state structures can all be classified as having the topology characteristic of an SH3 domain. Our results suggest a mechanism for folding in which the formation of a network of interactions among a subset of hydrophobic residues ensures that the native topology is generated. Such a mechanism enables high fidelity in folding while minimizing the need to establish a large number of specific interactions in the conformational search.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Molecular Sequence Data
  • Protein Folding*
  • Protein Structure, Secondary
  • Sequence Homology, Amino Acid