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Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals

Journal Article · · eLife
DOI:https://doi.org/10.7554/eLife.23961· OSTI ID:1510248
 [1];  [1];  [1]
  1. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Pharmacology
+ Show Author Affiliations
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:
Cancer Prevention Research Institute of Texas (CPRIT); Croucher Foundation Scholarship; Leukemia and Lymphoma Society Scholar Award; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); University of Texas Southwestern Endowed Scholars Program; Welch Foundation
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1510248
Journal Information:
eLife, Journal Name: eLife Journal Issue: 03, 2017 Vol. 6; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (10)

Engineering chromosome region maintenance 1 fragments that bind to nuclear export signals journal September 2019
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
Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore posted_content November 2017
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
Two Sides of the Coin: Ezrin/Radixin/Moesin and Merlin Control Membrane Structure and Contact Inhibition journal April 2019
Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore journal May 2018

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