A Highly Strained Nuclear Conformation of the Exportin Cse1p Revealed by Molecular Dynamics Simulations

Ulrich Zachariae, Helmut Grubmüller (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1469-1478
Number of pages10
JournalStructure
Volume14
Issue number9
Early online date12 Sep 2006
DOIs
Publication statusPublished - Sep 2006

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