An allosteric mechanism to displace nuclear export cargo from CRM1 and RanGTP by RanBP1

Masako Koyama, Yoshiyuki Matsuura

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The karyopherin CRM1 mediates nuclear export of proteins and ribonucleoproteins bearing a leucine-rich nuclear export signal (NES). To elucidate the precise mechanism by which NES-cargos are dissociated from CRM1 in the cytoplasm, which is important for transport directionality, we determined a 2.0-resolution crystal structure of yeast CRM1:RanBP1:RanGTP complex, an intermediate in the disassembly of the CRM1 nuclear export complex. The structure shows that on association of Ran-binding domain (RanBD) of RanBP1 with CRM1:NES-cargo:RanGTP complex, RanBD and the C-terminal acidic tail of Ran induce a large movement of the intra-HEAT9 loop of CRM1. The loop moves to the CRM1 inner surface immediately behind the NES-binding site and causes conformational rearrangements in HEAT repeats 11 and 12 so that the hydrophobic NES-binding cleft on the CRM1 outer surface closes, squeezing out the NES-cargo. This allosteric mechanism accelerates dissociation of NES by over two orders of magnitude. Structure-based mutagenesis indicated that the HEAT9 loop also functions as an allosteric autoinhibitor to stabilize CRM1 in a conformation that is unable to bind NES-cargo in the absence of RanGTP.

Original languageEnglish
Pages (from-to)2002-2013
Number of pages12
JournalEMBO Journal
Volume29
Issue number12
DOIs
Publication statusPublished - 2010 Jun 16
Externally publishedYes

Fingerprint

Nuclear Export Signals
Cell Nucleus Active Transport
Bearings (structural)
Karyopherins
Mutagenesis
Ribonucleoproteins
Leucine
Yeast
Conformations
Crystal structure
Binding Sites
Association reactions
Proteins
Nuclear Proteins
Cytoplasm
Yeasts

Keywords

  • CRM1
  • Exportin
  • NES
  • Nuclear export
  • RanBP1

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

An allosteric mechanism to displace nuclear export cargo from CRM1 and RanGTP by RanBP1. / Koyama, Masako; Matsuura, Yoshiyuki.

In: EMBO Journal, Vol. 29, No. 12, 16.06.2010, p. 2002-2013.

Research output: Contribution to journalArticle

Koyama, Masako ; Matsuura, Yoshiyuki. / An allosteric mechanism to displace nuclear export cargo from CRM1 and RanGTP by RanBP1. In: EMBO Journal. 2010 ; Vol. 29, No. 12. pp. 2002-2013.
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