Structural basis for leucine-rich nuclear export signal recognition by CRM1

Xiuhua Dong, Anindita Biswas, Katherine E. Süel, Laurie K. Jackson, Rita Martinez, Hongmei Gu, Yuh Min Chook

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

CRM1 (also known as XPO1 and exportin 1) mediates nuclear export of hundreds of proteins through the recognition of the leucine-rich nuclear export signal (LR-NES). Here we present the 2.9 structure of CRM1 bound to snurportin 1 (SNUPN). Snurportin 1 binds CRM1 in a bipartite manner by means of an amino-terminal LR-NES and its nucleotide-binding domain. The LR-NES is a combined α-helical-extended structure that occupies a hydrophobic groove between two CRM1 outer helices. The LR-NES interface explains the consensus hydrophobic pattern, preference for intervening electronegative residues and inhibition by leptomycin B. The second nuclear export signal epitope is a basic surface on the snurportin 1 nucleotide-binding domain, which binds an acidic patch on CRM1 adjacent to the LR-NES site. Multipartite recognition of individually weak nuclear export signal epitopes may be common to CRM1 substrates, enhancing CRM1 binding beyond the generally low affinity LR-NES. Similar energetic construction is also used in multipartite nuclear localization signals to provide broad substrate specificity and rapid evolution in nuclear transport.

Original languageEnglish (US)
Pages (from-to)1136-1141
Number of pages6
JournalNature
Volume458
Issue number7242
DOIs
StatePublished - Apr 30 2009

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Nuclear Export Signals
Leucine
Cell Nucleus Active Transport
Epitopes
Nucleotides
Nuclear Localization Signals
Substrate Specificity

ASJC Scopus subject areas

  • General

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Dong, X., Biswas, A., Süel, K. E., Jackson, L. K., Martinez, R., Gu, H., & Chook, Y. M. (2009). Structural basis for leucine-rich nuclear export signal recognition by CRM1. Nature, 458(7242), 1136-1141. https://doi.org/10.1038/nature07975

Structural basis for leucine-rich nuclear export signal recognition by CRM1. / Dong, Xiuhua; Biswas, Anindita; Süel, Katherine E.; Jackson, Laurie K.; Martinez, Rita; Gu, Hongmei; Chook, Yuh Min.

In: Nature, Vol. 458, No. 7242, 30.04.2009, p. 1136-1141.

Research output: Contribution to journalArticle

Dong, X, Biswas, A, Süel, KE, Jackson, LK, Martinez, R, Gu, H & Chook, YM 2009, 'Structural basis for leucine-rich nuclear export signal recognition by CRM1', Nature, vol. 458, no. 7242, pp. 1136-1141. https://doi.org/10.1038/nature07975
Dong X, Biswas A, Süel KE, Jackson LK, Martinez R, Gu H et al. Structural basis for leucine-rich nuclear export signal recognition by CRM1. Nature. 2009 Apr 30;458(7242):1136-1141. https://doi.org/10.1038/nature07975
Dong, Xiuhua ; Biswas, Anindita ; Süel, Katherine E. ; Jackson, Laurie K. ; Martinez, Rita ; Gu, Hongmei ; Chook, Yuh Min. / Structural basis for leucine-rich nuclear export signal recognition by CRM1. In: Nature. 2009 ; Vol. 458, No. 7242. pp. 1136-1141.
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