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Cofactor dependent conformational switching of GTPases

Hauryliuk, Vasili LU orcid ; Hansson, Sebastian LU and Ehrenberg, Måns (2008) In Biophysical Journal 95(4). p.1704-1715
Abstract

This theoretical work covers structural and biochemical aspects of nucleotide binding and GDP/GTP exchange of GTP hydrolases belonging to the family of small GTPases. Current models of GDP/GTP exchange regulation are often based on two specific assumptions. The first is that the conformation of a GTPase is switched by the exchange of the bound nucleotide from GDP to GTP or vice versa. The second is that GDP/GTP exchange is regulated by a guanine nucleotide exchange factor, which stabilizes a GTPase conformation with low nucleotide affinity. Since, however, recent biochemical and structural data seem to contradict this view, we present a generalized scheme for GTPase action. This novel ansatz accounts for those important cases when... (More)

This theoretical work covers structural and biochemical aspects of nucleotide binding and GDP/GTP exchange of GTP hydrolases belonging to the family of small GTPases. Current models of GDP/GTP exchange regulation are often based on two specific assumptions. The first is that the conformation of a GTPase is switched by the exchange of the bound nucleotide from GDP to GTP or vice versa. The second is that GDP/GTP exchange is regulated by a guanine nucleotide exchange factor, which stabilizes a GTPase conformation with low nucleotide affinity. Since, however, recent biochemical and structural data seem to contradict this view, we present a generalized scheme for GTPase action. This novel ansatz accounts for those important cases when conformational switching in addition to guanine nucleotide exchange requires the presence of cofactors, and gives a more nuanced picture of how the nucleotide exchange is regulated. The scheme is also used to discuss some problems of interpretation that may arise when guanine nucleotide exchange mechanisms are inferred from experiments with analogs of GTP, like GDPNP, GDPCP, and GDP γ S.

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author
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type
Contribution to journal
publication status
published
in
Biophysical Journal
volume
95
issue
4
pages
12 pages
publisher
Cell Press
external identifiers
  • pmid:18502805
  • scopus:50349097986
ISSN
0006-3495
DOI
10.1529/biophysj.107.127290
language
English
LU publication?
no
additional info
Funding Information: This work was supported by the Swedish Research Council, National Institutes of Health grant RO1 GM070768, and the Swedish Research Council (M.E.). Figs. 1 and 3 were made using PyMOL ( http://www.pymol.org ). Copyright: Copyright 2017 Elsevier B.V., All rights reserved.
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@article{ae2322ed-6ad1-439b-8af5-f7b5655fb775,
  abstract     = {{<p>This theoretical work covers structural and biochemical aspects of nucleotide binding and GDP/GTP exchange of GTP hydrolases belonging to the family of small GTPases. Current models of GDP/GTP exchange regulation are often based on two specific assumptions. The first is that the conformation of a GTPase is switched by the exchange of the bound nucleotide from GDP to GTP or vice versa. The second is that GDP/GTP exchange is regulated by a guanine nucleotide exchange factor, which stabilizes a GTPase conformation with low nucleotide affinity. Since, however, recent biochemical and structural data seem to contradict this view, we present a generalized scheme for GTPase action. This novel ansatz accounts for those important cases when conformational switching in addition to guanine nucleotide exchange requires the presence of cofactors, and gives a more nuanced picture of how the nucleotide exchange is regulated. The scheme is also used to discuss some problems of interpretation that may arise when guanine nucleotide exchange mechanisms are inferred from experiments with analogs of GTP, like GDPNP, GDPCP, and GDP γ S.</p>}},
  author       = {{Hauryliuk, Vasili and Hansson, Sebastian and Ehrenberg, Måns}},
  issn         = {{0006-3495}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{4}},
  pages        = {{1704--1715}},
  publisher    = {{Cell Press}},
  series       = {{Biophysical Journal}},
  title        = {{Cofactor dependent conformational switching of GTPases}},
  url          = {{http://dx.doi.org/10.1529/biophysj.107.127290}},
  doi          = {{10.1529/biophysj.107.127290}},
  volume       = {{95}},
  year         = {{2008}},
}