3M1I

Crystal structure of yeast CRM1 (Xpo1p) in complex with yeast RanBP1 (Yrb1p) and yeast RanGTP (Gsp1pGTP)

3M1I の概要

• エントリーDOI: 10.2210/pdb3m1i/pdb
• 分子名称: GTP-binding nuclear protein GSP1/CNR1, Ran-specific GTPase-activating protein 1, Exportin-1, ... (6 entities in total)
• 機能のキーワード: heat repeat, exportin, gtp-binding, nucleotide-binding, nucleus, protein transport, transport, gtpase activation
• 由来する生物種: Saccharomyces cerevisiae (yeast); 詳細
• 細胞内の位置: Nucleus: P32835 P30822; Cytoplasm: P41920
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 167664.83

構造登録者

Koyama, M.,Matsuura, Y. (登録日: 2010-03-05, 公開日: 2010-06-02, 最終更新日: 2023-11-01)

主引用文献

Koyama, M.,Matsuura, Y.
An allosteric mechanism to displace nuclear export cargo from CRM1 and RanGTP by RanBP1
Embo J., 29:2002-2013, 2010

PubMed 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-A 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.

PubMed: 20485264
DOI: 10.1038/emboj.2010.89

実験手法

X-RAY DIFFRACTION (2 Å)