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Title: Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals

Journal Article · · eLife
ORCiD logo [1];  [1]; ORCiD logo [1]
  1. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Pharmacology
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Nuclear export receptor CRM1 binds highly variable nuclear export signals (NESs) in hundreds of different cargoes. Previously we have shown that CRM1 binds NESs in both polypeptide orientations. Here, we show crystal structures of CRM1 bound to eight additional NESs which reveal diverse conformations that range from loop-like to all-helix, which occupy different extents of the invariant NES-binding groove. Analysis of all NES structures show 5-6 distinct backbone conformations where the only conserved secondary structural element is one turn of helix that binds the central portion of the CRM1 groove. All NESs also participate in main chain hydrogen bonding with human CRM1 Lys568 side chain, which acts as a specificity filter that prevents binding of non-NES peptides. The large conformational range of NES backbones explains the lack of a fixed pattern for its 3-5 hydrophobic anchor residues, which in turn explains the large array of peptide sequences that can function as NESs.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); Cancer Prevention Research Institute of Texas (CPRIT); Welch Foundation; Leukemia and Lymphoma Society Scholar Award; University of Texas Southwestern Endowed Scholars Program; Croucher Foundation Scholarship
Grant/Contract Number:
AC02-06CH11357; RP120352; RP150053; R01 GM069909; I-1532
OSTI ID:
1510248
Journal Information:
eLife, Vol. 6, Issue 03, 2017; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Active nuclear import and passive nuclear export are the primary determinants of TDP-43 localization journal May 2018
Structural prerequisites for CRM1-dependent nuclear export signaling peptides: accessibility, adapting conformation, and the stability at the binding site journal April 2019
Nuclear export of ubiquitinated proteins via the UBIN-POST system journal April 2018
Role of a versatile peptide motif in controlling Hox nuclear export and autophagy in the Drosophila fat body posted_content November 2019
NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals journal February 2018
Viral Appropriation: Laying Claim to Host Nuclear Transport Machinery journal June 2019
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