Cooperative formation of native-like tertiary contacts in the ensemble of unfolded states of a four-helix protein

TY - JOUR

T1 - Cooperative formation of native-like tertiary contacts in the ensemble of unfolded states of a four-helix protein

AU - Bruun, Susanne W

AU - Iesmantavicius, Vytautas

AU - Danielsson, Jens

AU - Poulsen, Flemming Martin

PY - 2010/7/27

Y1 - 2010/7/27

N2 - In studies of the ensembles of unfolded structures of a four-helix bundle protein, we have detected the presence of potential precursors of native tertiary structures. These observations were based on the perturbation of NMR chemical shifts of the protein backbone atoms by single site mutations. Some mutations change the chemical shifts of residues remote from the site of mutation indicating the presence of an interaction between the mutated and the remote residues, suggesting that the formation of helix segments and helix-helix interactions is cooperative. We can begin to track down the folding mechanism of this protein using only experimental data by combining the information available for the rate limiting structure formation during the folding process with measurements of the site specific hydrogen bond formation in the burst phase, and with the existence prior to the folding reaction of tertiary structures in the ensemble of otherwise unfolded structures observed in the present study.

AB - In studies of the ensembles of unfolded structures of a four-helix bundle protein, we have detected the presence of potential precursors of native tertiary structures. These observations were based on the perturbation of NMR chemical shifts of the protein backbone atoms by single site mutations. Some mutations change the chemical shifts of residues remote from the site of mutation indicating the presence of an interaction between the mutated and the remote residues, suggesting that the formation of helix segments and helix-helix interactions is cooperative. We can begin to track down the folding mechanism of this protein using only experimental data by combining the information available for the rate limiting structure formation during the folding process with measurements of the site specific hydrogen bond formation in the burst phase, and with the existence prior to the folding reaction of tertiary structures in the ensemble of otherwise unfolded structures observed in the present study.

KW - Animals

KW - Cattle

KW - Diazepam Binding Inhibitor

KW - Hydrogen Bonding

KW - Hydrogen-Ion Concentration

KW - Magnetic Resonance Spectroscopy

KW - Models, Molecular

KW - Mutation

KW - Protein Conformation

KW - Protein Folding

KW - Protein Structure, Secondary

KW - Proteins

U2 - 10.1073/pnas.1003004107

DO - 10.1073/pnas.1003004107

M3 - Journal article

C2 - 20624986

SN - 0027-8424

VL - 107

SP - 13306

EP - 13311

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 30

ER -