A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function

Erik Thomas Dustrude, Samantha Perez-Miller, Liberty François-Moutal, Aubin Moutal, May Khanna, Rajesh Khanna

Research output: Research - peer-reviewArticle

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Abstract

The neuronal collapsin response mediator protein 2 (CRMP2) undergoes several posttranslational modifications that codify its functions. Most recently, CRMP2 SUMOylation (addition of small ubiquitin like modifier (SUMO)) was identified as a key regulatory step within a modification program that codes for CRMP2 interaction with, and trafficking of, voltage-gated sodium channel NaV1.7. In this paper, we illustrate the utility of combining sequence alignment within protein families with structural analysis to identify, from several putative SUMOylation sites, those that are most likely to be biologically relevant. Co-opting this principle to CRMP2, we demonstrate that, of 3 sites predicted to be SUMOylated in CRMP2, only the lysine 374 site is a SUMOylation client. A reduction in NaV1.7 currents was the corollary of the loss of CRMP2 SUMOylation at this site. A 1.78-Å-resolution crystal structure of mouse CRMP2 was solved using X-ray crystallography, revealing lysine 374 as buried within the CRMP2 tetramer interface but exposed in the monomer. Since CRMP2 SUMOylation is dependent on phosphorylation, we postulate that this state forces CRMP2 toward a monomer, exposing the SUMO site and consequently, resulting in constitutive regulation of NaV1.7.

LanguageEnglish (US)
Pages1-13
Number of pages13
JournalChannels
DOIs
StateAccepted/In press - Mar 24 2017

Fingerprint

Sumoylation
collapsin response mediator protein-2
Ubiquitin
Lysine
Monomers
NAV1.7 Voltage-Gated Sodium Channel
Sequence Alignment
X Ray Crystallography
Post Translational Protein Processing
Phosphorylation
Proteins
X ray crystallography
Structural analysis
Crystal structure

Keywords

  • CRMP2
  • NaV1.7
  • post-translational modifications
  • SUMOylation
  • trafficking
  • X-ray crystallography

ASJC Scopus subject areas

  • Biophysics
  • Medicine(all)
  • Biochemistry

Cite this

A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function. / Dustrude, Erik Thomas; Perez-Miller, Samantha; François-Moutal, Liberty; Moutal, Aubin; Khanna, May; Khanna, Rajesh.

In: Channels, 24.03.2017, p. 1-13.

Research output: Research - peer-reviewArticle

Dustrude ET, Perez-Miller S, François-Moutal L, Moutal A, Khanna M, Khanna R. A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function. Channels. 2017 Mar 24;1-13. Available from, DOI: 10.1080/19336950.2017.1299838
Dustrude, Erik Thomas ; Perez-Miller, Samantha ; François-Moutal, Liberty ; Moutal, Aubin ; Khanna, May ; Khanna, Rajesh. / A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function. In: Channels. 2017 ; pp. 1-13
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