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

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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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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