A highly strained nuclear conformation of the exportin Cse1p revealed by molecular dynamics simulations.
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-alpha 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.
Zachariae
Ulrich
U
Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Grubmüller
Helmut
H
D002467:Cell Nucleus / Q000737:chemistry*; D028884:Karyopherins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D055672:Static Electricity
D028884:Karyopherins