TY - JOUR
T1 - A Highly Strained Nuclear Conformation of the Exportin Cse1p Revealed by Molecular Dynamics Simulations
AU - Zachariae, Ulrich
AU - Grubmüller, Helmut
N1 - Funding Information:
We thank Dirk Görlich, Peter Hinterdorfer, Ziv Reich, Matthias Müller, Carsten Kutzner, and Marcus Kubitzki for stimulating discussions. This work was supported by the Human Frontier Science Program (Grant RGP 53/2004).
Copyright:
© 2006 Elsevier Ltd. All rights reserved.
PY - 2006/9
Y1 - 2006/9
N2 - To investigate the stability of the open nuclear state of the exportin Cse1p and its closing mechanism at the atomic level, we have performed multiple molecular dynamics simulations. The simulations revealed a strikingly fast transition of Cse1p from the open conformation to the closed cytoplasmic form, consistent with the proposal that Cse1p represents a "spring-loaded molecule." The structure of the ring-shaped state obtained in the simulations is remarkably close to the crystal structure of the cytoplasmic state, though the open nuclear structure was used as the only input. The conformational change is initially driven by release of strain due to RanGTP/importin-α binding. Subsequently, a stable closed state is formed, driven by attraction of electrostatically complementary interfaces. These results are consistent with and extend previous proposals. Reverse-charge and neutral mutants remained in an open state. The simulations predict a detailed reaction pathway and resolve the role of suggested hinge regions.
AB - To investigate the stability of the open nuclear state of the exportin Cse1p and its closing mechanism at the atomic level, we have performed multiple molecular dynamics simulations. The simulations revealed a strikingly fast transition of Cse1p from the open conformation to the closed cytoplasmic form, consistent with the proposal that Cse1p represents a "spring-loaded molecule." The structure of the ring-shaped state obtained in the simulations is remarkably close to the crystal structure of the cytoplasmic state, though the open nuclear structure was used as the only input. The conformational change is initially driven by release of strain due to RanGTP/importin-α binding. Subsequently, a stable closed state is formed, driven by attraction of electrostatically complementary interfaces. These results are consistent with and extend previous proposals. Reverse-charge and neutral mutants remained in an open state. The simulations predict a detailed reaction pathway and resolve the role of suggested hinge regions.
UR - http://www.scopus.com/inward/record.url?scp=33748305808&partnerID=8YFLogxK
U2 - 10.1016/j.str.2006.08.001
DO - 10.1016/j.str.2006.08.001
M3 - Article
C2 - 16962977
AN - SCOPUS:33748305808
SN - 0969-2126
VL - 14
SP - 1469
EP - 1478
JO - Structure
JF - Structure
IS - 9
ER -