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Time Scales of Conformational Gating in a Lipid-Binding Protein

Kaieda, Shuji LU and Halle, Bertil LU (2015) In The Journal of Physical Chemistry Part B 119(25). p.7957-7967
Abstract
Lipid-binding proteins Sequester amphiphilic molecules in a large internal : cavity occupied by similar to 30 water molecules, some of which are displaced by the ligand. The role; of these internal water molecules in lipid binding and release is not understood. We use magnetic relaxation dispersion (MRD) to directly monitor internal-water dynamics in apo and palmitate-bound rat intestinal fatty acid-binding protein (rIFABP). Specifically, we record the water H-2 and O-17 MRD profiles of the apo and hobo forms of rIFABP in solution or immobilized by covalent cross-links. A global analysis of this extensive data set identifies three internal-water classes with mean survival times of similar to 1 ns, similar to 100 ns, and similar to 6 mu s.... (More)
Lipid-binding proteins Sequester amphiphilic molecules in a large internal : cavity occupied by similar to 30 water molecules, some of which are displaced by the ligand. The role; of these internal water molecules in lipid binding and release is not understood. We use magnetic relaxation dispersion (MRD) to directly monitor internal-water dynamics in apo and palmitate-bound rat intestinal fatty acid-binding protein (rIFABP). Specifically, we record the water H-2 and O-17 MRD profiles of the apo and hobo forms of rIFABP in solution or immobilized by covalent cross-links. A global analysis of this extensive data set identifies three internal-water classes with mean survival times of similar to 1 ns, similar to 100 ns, and similar to 6 mu s. We associate the two longer time scales with conformational fluctuations of the gap between beta-strands D and E (similar to 6 mu s) and of the portal at the helix-capped end of the beta-barrel (similar to 100 ns). These fluctuations limit the exchange rates of a few highly ordered structural water molecules but not the dissociation rate of the fatty acid. The remaining 90% (apo) or 70% (hobo) of cavity waters exchange among internal hydration sites on a time scale of similar to 1 ns but exhibit substantial orientational order, particularly in the holo form. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of Physical Chemistry Part B
volume
119
issue
25
pages
7957 - 7967
publisher
The American Chemical Society
external identifiers
  • wos:000357139800018
  • scopus:84933056912
ISSN
1520-5207
DOI
10.1021/acs.jpcb.5b03214
language
English
LU publication?
yes
id
5dcb397b-e0de-4018-967f-5bfd9b220093 (old id 7791086)
date added to LUP
2015-09-02 10:43:50
date last changed
2017-09-24 03:55:28
@article{5dcb397b-e0de-4018-967f-5bfd9b220093,
  abstract     = {Lipid-binding proteins Sequester amphiphilic molecules in a large internal : cavity occupied by similar to 30 water molecules, some of which are displaced by the ligand. The role; of these internal water molecules in lipid binding and release is not understood. We use magnetic relaxation dispersion (MRD) to directly monitor internal-water dynamics in apo and palmitate-bound rat intestinal fatty acid-binding protein (rIFABP). Specifically, we record the water H-2 and O-17 MRD profiles of the apo and hobo forms of rIFABP in solution or immobilized by covalent cross-links. A global analysis of this extensive data set identifies three internal-water classes with mean survival times of similar to 1 ns, similar to 100 ns, and similar to 6 mu s. We associate the two longer time scales with conformational fluctuations of the gap between beta-strands D and E (similar to 6 mu s) and of the portal at the helix-capped end of the beta-barrel (similar to 100 ns). These fluctuations limit the exchange rates of a few highly ordered structural water molecules but not the dissociation rate of the fatty acid. The remaining 90% (apo) or 70% (hobo) of cavity waters exchange among internal hydration sites on a time scale of similar to 1 ns but exhibit substantial orientational order, particularly in the holo form.},
  author       = {Kaieda, Shuji and Halle, Bertil},
  issn         = {1520-5207},
  language     = {eng},
  number       = {25},
  pages        = {7957--7967},
  publisher    = {The American Chemical Society},
  series       = {The Journal of Physical Chemistry Part B},
  title        = {Time Scales of Conformational Gating in a Lipid-Binding Protein},
  url          = {http://dx.doi.org/10.1021/acs.jpcb.5b03214},
  volume       = {119},
  year         = {2015},
}