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Correlated dynamics of consecutive residues reveal transient and cooperative unfolding of secondary structure in proteins

Lundström, Patrik LU ; Mulder, Frans LU and Akke, Mikael LU (2005) In Proceedings of the National Academy of Sciences 102(47). p.16984-16989
Abstract
Nuclear spin relaxation is a powerful method for studying molecular dynamics at atomic resolution. Recent methods development in biomolecular NMR spectroscopy has enabled detailed investigations of molecular dynamics that are critical for biological function, with prominent examples addressing allostery, enzyme catalysis, and protein folding. Dynamic processes with similar correlation times are often detected in multiple locations of the molecule, raising the question of whether the underlying motions are correlated (corresponding to concerted fluctuations involving many atoms distributed across extended regions of the molecule) or uncorrelated (corresponding to independent fluctuations involving few atoms in localized regions). Here, we... (More)
Nuclear spin relaxation is a powerful method for studying molecular dynamics at atomic resolution. Recent methods development in biomolecular NMR spectroscopy has enabled detailed investigations of molecular dynamics that are critical for biological function, with prominent examples addressing allostery, enzyme catalysis, and protein folding. Dynamic processes with similar correlation times are often detected in multiple locations of the molecule, raising the question of whether the underlying motions are correlated (corresponding to concerted fluctuations involving many atoms distributed across extended regions of the molecule) or uncorrelated (corresponding to independent fluctuations involving few atoms in localized regions). Here, we have used C-13(alpha)(i - 1)/C-13(alpha)(i) differential multiple-quantum spin relaxation to provide direct evidence for correlated dynamics of consecutive amino acid residues in the protein sequence. By monitoring overlapping pairs of residues (i - 1 and i, i and i + 1, etc.), we identified correlated motions that extend through continuous segments of the sequence. We detected significant correlated conformational transitions in the native state of the E140Q mutant of the calmodulin C-terminal domain. Previous work has shown that this domain exchanges between two major conformational states that resemble the functionally relevant open and closed states of the WT protein, with a mean correlation time of approximate to 20 mu s. The present results reveal that an entire alpha-helix undergoes partial unraveling in a transient and cooperative manner. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
102
issue
47
pages
16984 - 16989
publisher
National Acad Sciences
external identifiers
  • wos:000233463200016
  • scopus:28044463992
ISSN
1091-6490
DOI
10.1073/pnas.0504361102
language
English
LU publication?
yes
id
ca574b8e-e1be-4ddd-8233-d913cc6e8de7 (old id 151481)
date added to LUP
2007-06-29 13:22:06
date last changed
2017-04-30 07:38:03
@article{ca574b8e-e1be-4ddd-8233-d913cc6e8de7,
  abstract     = {Nuclear spin relaxation is a powerful method for studying molecular dynamics at atomic resolution. Recent methods development in biomolecular NMR spectroscopy has enabled detailed investigations of molecular dynamics that are critical for biological function, with prominent examples addressing allostery, enzyme catalysis, and protein folding. Dynamic processes with similar correlation times are often detected in multiple locations of the molecule, raising the question of whether the underlying motions are correlated (corresponding to concerted fluctuations involving many atoms distributed across extended regions of the molecule) or uncorrelated (corresponding to independent fluctuations involving few atoms in localized regions). Here, we have used C-13(alpha)(i - 1)/C-13(alpha)(i) differential multiple-quantum spin relaxation to provide direct evidence for correlated dynamics of consecutive amino acid residues in the protein sequence. By monitoring overlapping pairs of residues (i - 1 and i, i and i + 1, etc.), we identified correlated motions that extend through continuous segments of the sequence. We detected significant correlated conformational transitions in the native state of the E140Q mutant of the calmodulin C-terminal domain. Previous work has shown that this domain exchanges between two major conformational states that resemble the functionally relevant open and closed states of the WT protein, with a mean correlation time of approximate to 20 mu s. The present results reveal that an entire alpha-helix undergoes partial unraveling in a transient and cooperative manner.},
  author       = {Lundström, Patrik and Mulder, Frans and Akke, Mikael},
  issn         = {1091-6490},
  language     = {eng},
  number       = {47},
  pages        = {16984--16989},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Correlated dynamics of consecutive residues reveal transient and cooperative unfolding of secondary structure in proteins},
  url          = {http://dx.doi.org/10.1073/pnas.0504361102},
  volume       = {102},
  year         = {2005},
}