title: Structural basis for leucine-rich nuclear export signal recognition by CRM1.
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 A 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 alpha-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.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Dong
authors.forename: Anindita
authors.initials: A
authors.lastname: Biswas
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Süel
authors.forename: Laurie K
authors.initials: LK
authors.lastname: Jackson
authors.forename: Rita
authors.initials: R
authors.lastname: Martinez
authors.forename: Hongmei
authors.initials: H
authors.lastname: Gu
authors.forename: Yuh Min
authors.initials: YM
authors.lastname: Chook