5UQC

Crystal structure of mouse CRMP2

5UQC の概要

• エントリーDOI: 10.2210/pdb5uqc/pdb
• 分子名称: Dihydropyrimidinase-related protein 2, 2-(2-{2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHANOL (3 entities in total)
• 機能のキーワード: sumoylation, transcription, signaling protein
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Cytoplasm, cytosol : O08553
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 106019.56

構造登録者

Khanna, M.,Khanna, R.,Perez-Miller, S.,Francois-Moutal, L. (登録日: 2017-02-07, 公開日: 2017-03-22, 最終更新日: 2023-10-04)

主引用文献

Dustrude, E.T.,Perez-Miller, S.,Francois-Moutal, L.,Moutal, A.,Khanna, M.,Khanna, R.
A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function.
Channels (Austin), 11:316-328, 2017

PubMed 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.

PubMed: 28277940
DOI: 10.1080/19336950.2017.1299838

実験手法

X-RAY DIFFRACTION (1.78 Å)