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

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.

journal_name

Nat Struct Mol Biol

authors

Lindorff-Larsen K,Vendruscolo M,Paci E,Dobson CM

doi

10.1038/nsmb765

keywords:

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

443-9

issue

5

eissn

1545-9993

issn

1545-9985

pii

nsmb765

journal_volume

11

pub_type

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