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Alternative Explanations for "Multistate" Kinetics in Protein Folding: Transient Aggregation and Changing Transition-State Ensembles

Oliveberg, Mikael LU (1998) In Accounts of Chemical Research 31(11). p.765-772
Abstract
Deviations from classical two-state kinetics in protein folding need not always be explained by the presence of rapidly formed intermediates. In some cases, such deviations are caused by short-lived aggregates whereas in other cases they arise from changes of the position of the transition state. These are two new facets of the mechanism of two-state folding. The first part of this account describes the effect of aggregates which form transiently in the first few milliseconds of the refolding reaction. The aggregates show many similarities with folding intermediates, but may be identified by their disappearance at low concentrations of protein where the two-state conversion of monomeric protein becomes predominant. In the second part, the... (More)
Deviations from classical two-state kinetics in protein folding need not always be explained by the presence of rapidly formed intermediates. In some cases, such deviations are caused by short-lived aggregates whereas in other cases they arise from changes of the position of the transition state. These are two new facets of the mechanism of two-state folding. The first part of this account describes the effect of aggregates which form transiently in the first few milliseconds of the refolding reaction. The aggregates show many similarities with folding intermediates, but may be identified by their disappearance at low concentrations of protein where the two-state conversion of monomeric protein becomes predominant. In the second part, the focus is directed to two-state folding and movements of the transition state ensemble. The movements are used to derive information about the shape of the free-energy profile for folding. It emerges from a comparison of the kinetic behaviour of several small model proteins that the free-energy barrier for folding could be generally broad and level. An attractive feature of broad barriers is that, depending on minor variations in the fine-structure of the free-energy profile, they account for a wide range of seemingly unrelated folding data, including deviations from classical two-state kinetics determined by free-energy extrapolations. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Accounts of Chemical Research
volume
31
issue
11
pages
765 - 772
publisher
The American Chemical Society
external identifiers
  • scopus:0000384736
ISSN
1520-4898
DOI
10.1021/ar970089m
language
English
LU publication?
yes
id
bd3a2ddb-8a6a-41d0-bc24-12057ddf2bd3 (old id 125583)
date added to LUP
2007-07-09 08:41:43
date last changed
2017-07-30 04:42:58
@article{bd3a2ddb-8a6a-41d0-bc24-12057ddf2bd3,
  abstract     = {Deviations from classical two-state kinetics in protein folding need not always be explained by the presence of rapidly formed intermediates. In some cases, such deviations are caused by short-lived aggregates whereas in other cases they arise from changes of the position of the transition state. These are two new facets of the mechanism of two-state folding. The first part of this account describes the effect of aggregates which form transiently in the first few milliseconds of the refolding reaction. The aggregates show many similarities with folding intermediates, but may be identified by their disappearance at low concentrations of protein where the two-state conversion of monomeric protein becomes predominant. In the second part, the focus is directed to two-state folding and movements of the transition state ensemble. The movements are used to derive information about the shape of the free-energy profile for folding. It emerges from a comparison of the kinetic behaviour of several small model proteins that the free-energy barrier for folding could be generally broad and level. An attractive feature of broad barriers is that, depending on minor variations in the fine-structure of the free-energy profile, they account for a wide range of seemingly unrelated folding data, including deviations from classical two-state kinetics determined by free-energy extrapolations.},
  author       = {Oliveberg, Mikael},
  issn         = {1520-4898},
  language     = {eng},
  number       = {11},
  pages        = {765--772},
  publisher    = {The American Chemical Society},
  series       = {Accounts of Chemical Research},
  title        = {Alternative Explanations for "Multistate" Kinetics in Protein Folding: Transient Aggregation and Changing Transition-State Ensembles},
  url          = {http://dx.doi.org/10.1021/ar970089m},
  volume       = {31},
  year         = {1998},
}