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Functional dynamics of human FKBP12 revealed by methyl C-13 rotating frame relaxation dispersion NMR spectroscopy

Brath, Ulrika LU ; Akke, Mikael LU orcid ; Yang, DW ; Kay, LE and Mulder, Frans LU (2006) In Journal of the American Chemical Society 128(17). p.5718-5727
Abstract
Transverse relaxation dispersion NMR spectroscopy can provide atom-specific information about time scales, populations, and the extent of structural reorganization in proteins under equilibrium conditions. A method is described that uses side-chain methyl groups as local reporters for conformational transitions taking place in the microsecond regime. The experiment measures carbon nuclear spin relaxation rates in the presence of continuous wave off-resonance irradiation, in proteins uniformly enriched with C-13, and partially randomly labeled with 2 H. The method was applied to human FK-506 binding protein (FKBP12), which uses a common surface for binding substrates in its dual role as both an immunophilin and folding assistant.... (More)
Transverse relaxation dispersion NMR spectroscopy can provide atom-specific information about time scales, populations, and the extent of structural reorganization in proteins under equilibrium conditions. A method is described that uses side-chain methyl groups as local reporters for conformational transitions taking place in the microsecond regime. The experiment measures carbon nuclear spin relaxation rates in the presence of continuous wave off-resonance irradiation, in proteins uniformly enriched with C-13, and partially randomly labeled with 2 H. The method was applied to human FK-506 binding protein (FKBP12), which uses a common surface for binding substrates in its dual role as both an immunophilin and folding assistant. Conformational dynamics on a time scale of similar to 130 mu s were detected for methyl groups located in the substrate binding pocket, demonstrating its plasticity in the absence of substrate. The spatial arrangement of affected side-chain atoms suggests that substrate recognition involves the rapid relative movement of the subdomain comprising residues Ala81-Thr96 and that the observed dynamics play an important role in facilitating the interaction of this protein with its many partners, including calcineurin. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Chemical Society
volume
128
issue
17
pages
5718 - 5727
publisher
The American Chemical Society (ACS)
external identifiers
  • wos:000237389900042
  • scopus:33646557015
ISSN
1520-5126
DOI
10.1021/ja0570279
language
English
LU publication?
yes
id
2e590625-1183-4f71-b7e8-fbb2b2c2c245 (old id 410018)
date added to LUP
2016-04-01 16:21:41
date last changed
2022-01-28 19:12:12
@article{2e590625-1183-4f71-b7e8-fbb2b2c2c245,
  abstract     = {{Transverse relaxation dispersion NMR spectroscopy can provide atom-specific information about time scales, populations, and the extent of structural reorganization in proteins under equilibrium conditions. A method is described that uses side-chain methyl groups as local reporters for conformational transitions taking place in the microsecond regime. The experiment measures carbon nuclear spin relaxation rates in the presence of continuous wave off-resonance irradiation, in proteins uniformly enriched with C-13, and partially randomly labeled with 2 H. The method was applied to human FK-506 binding protein (FKBP12), which uses a common surface for binding substrates in its dual role as both an immunophilin and folding assistant. Conformational dynamics on a time scale of similar to 130 mu s were detected for methyl groups located in the substrate binding pocket, demonstrating its plasticity in the absence of substrate. The spatial arrangement of affected side-chain atoms suggests that substrate recognition involves the rapid relative movement of the subdomain comprising residues Ala81-Thr96 and that the observed dynamics play an important role in facilitating the interaction of this protein with its many partners, including calcineurin.}},
  author       = {{Brath, Ulrika and Akke, Mikael and Yang, DW and Kay, LE and Mulder, Frans}},
  issn         = {{1520-5126}},
  language     = {{eng}},
  number       = {{17}},
  pages        = {{5718--5727}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of the American Chemical Society}},
  title        = {{Functional dynamics of human FKBP12 revealed by methyl C-13 rotating frame relaxation dispersion NMR spectroscopy}},
  url          = {{http://dx.doi.org/10.1021/ja0570279}},
  doi          = {{10.1021/ja0570279}},
  volume       = {{128}},
  year         = {{2006}},
}