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

Kresten Lindorff-Larsen; Michele Vendruscolo; Emanuele Paci; Christopher M Dobson

doi:10.1038/nsmb765

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

Kresten Lindorff-Larsen, Michele Vendruscolo, Emanuele Paci, Christopher M Dobson

81 Citations (Scopus)

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.

Original language	English
Journal	Nature Structural and Molecular Biology
Volume	11
Issue number	5
Pages (from-to)	443-9
Number of pages	7
ISSN	1545-9993
DOIs	https://doi.org/10.1038/nsmb765
Publication status	Published - 2004
Externally published	Yes

Access to Document

10.1038/nsmb765

Cite this

@article{1441ffd29dd948e295ed16935f311ef5,

title = "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.",

author = "Kresten Lindorff-Larsen and Michele Vendruscolo and Emanuele Paci and Dobson, {Christopher M}",

year = "2004",

doi = "10.1038/nsmb765",

language = "English",

volume = "11",

pages = "443--9",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

publisher = "nature publishing group",

number = "5",

}

TY - JOUR

T1 - Transition states for protein folding have native topologies despite high structural variability

AU - Lindorff-Larsen, Kresten

AU - Vendruscolo, Michele

AU - Paci, Emanuele

AU - Dobson, Christopher M

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1038/nsmb765

DO - 10.1038/nsmb765

M3 - Journal article

C2 - 15098020

SN - 1545-9993

VL - 11

SP - 443

EP - 449

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 5

ER -

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

Abstract

Access to Document

Fingerprint

Cite this