5ZNN

Crystal structure of ligand-free form of the Vps10 ectodomain of Sortilin

Summary for 5ZNN

• Entry DOI: 10.2210/pdb5znn/pdb
• Descriptor: Sortilin, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: cytokine trafficking, protein transport
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 155581.04

Authors

Yabe-Wada, T.,Unno, M. (deposition date: 2018-04-10, release date: 2018-07-18, Last modification date: 2025-09-17)

Primary citation

Yabe-Wada, T.,Matsuba, S.,Unno, M.,Onai, N.
Crystal structure of the ligand-free form of the Vps10 ectodomain of dimerized Sortilin at acidic pH
FEBS Lett., 592:2647-2657, 2018

PubMed Abstract: Sortilin is a multifunctional sorting receptor involved in cytokine production in immune cells. To understand the mechanism of Sortilin-mediated cytokine trafficking, we determined the 2.45-Å structure of the dimerized Sortilin ectodomain (sSortilin or the Vps10-domain) crystallized at acidic pH. Substantial conformational changes upon dimerization lead to the intermolecular hydrophobic interaction between the conserved E455 and F137. Analysis of the electrostatic surface and size-exclusion chromatography revealed that sSortilin dimerization occurs due to an increase in hydrophobic interactions at the neutral dimer interface at acidic pH. The N682-attached N-glycan in the vicinity of the dimer interface implies its involvement in the dimerization. The disruption of Sortilin dimerization by mutations impairs efficient interferon-alpha secretion from cells. These results suggest the functional importance of Sortilin dimerization in cytokine trafficking.

PubMed: 29972886
DOI: 10.1002/1873-3468.13181

Experimental method

X-RAY DIFFRACTION (2.448 Å)