Structural insights into how Yrb2p accelerates the assembly of the Xpo1p nuclear export complex

Masako Koyama, Natsuki Shirai, Yoshiyuki Matsuura

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Proteins and ribonucleoproteins containing a nuclear export signal (NES) assemble with the exportin Xpo1p (yeast CRM1) and Gsp1p-GTP (yeast Ran- GTP) in the nucleus and exit through the nuclear pore complex. In the cytoplasm, Yrb1p (yeast RanBP1) displaces NES from Xpo1p. Efficient export of NES-cargoes requires Yrb2p (yeast RanBP3), a primarily nuclear protein containing nucleoporinlike phenylalanine-glycine (FG) repeats and a low-affinity Gsp1p-binding domain (RanBD). Here, we show that Yrb2p strikingly accelerates the association of Gsp1p-GTP and NES to Xpo1p. We have solved the crystal structure of the Xpo1p-Yrb2p- Gsp1p-GTP complex, a key assembly intermediate that can bind cargo rapidly. Although the NES-binding cleft of Xpo1p is closed in this intermediate, our data suggest that preloading of Gsp1p-GTP onto Xpo1p by Yrb2p, conformational flexibility of Xpo1p, and the low affinity of RanBD enable active displacement of Yrb2p RanBD by NES to occur effectively. The structure also reveals the major binding sites for FG repeats on Xpo1p.

Original languageEnglish
Pages (from-to)983-995
Number of pages13
JournalCell Reports
Volume9
Issue number3
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Nuclear Export Signals
Cell Nucleus Active Transport
Guanosine Triphosphate
Yeast
Yeasts
Karyopherins
Ribonucleoproteins
Nuclear Proteins
Phenylalanine
Glycine
Nuclear Pore
Crystal structure
Binding Sites
Cytoplasm
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Structural insights into how Yrb2p accelerates the assembly of the Xpo1p nuclear export complex. / Koyama, Masako; Shirai, Natsuki; Matsuura, Yoshiyuki.

In: Cell Reports, Vol. 9, No. 3, 2014, p. 983-995.

Research output: Contribution to journalArticle

Koyama, Masako ; Shirai, Natsuki ; Matsuura, Yoshiyuki. / Structural insights into how Yrb2p accelerates the assembly of the Xpo1p nuclear export complex. In: Cell Reports. 2014 ; Vol. 9, No. 3. pp. 983-995.
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