NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1

Thomas Güttler, Tobias Madl, Piotr Neumann, Danilo Deichsel, Lorenzo Corsini, Thomas Monecke, Ralf Ficner, Michael Sattler, Dirk Görlich

Research output: Contribution to journalArticlepeer-review

198 Scopus citations

Abstract

Classic nuclear export signals (NESs) confer CRM1-dependent nuclear export. Here we present crystal structures of the RanGTP-'CRM1 complex alone and bound to the prototypic PKI or HIV-1 Rev NESs. These NESs differ markedly in the spacing of their key hydrophobic (■) residues, yet CRM1 recognizes them with the same rigid set of five ■ pockets. The different ■ spacings are compensated for by different conformations of the bound NESs: in the case of PKI, an -helical conformation, and in the case of Rev, an extended conformation with a critical proline docking into a ■ pocket. NMR analyses of CRM1-bound and CRM1-free PKI NES suggest that CRM1 selects NES conformers that pre-exist in solution. Our data lead to a new structure-based NES consensus, and explain why NESs differ in their affinities for CRM1 and why supraphysiological NESs bind the exportin so tightly.

Original languageEnglish
Pages (from-to)1367-1376
Number of pages10
JournalNature Structural and Molecular Biology
Volume17
Issue number11
DOIs
StatePublished - Nov 2010

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