5NMT

Dimer structure of Sortilin ectodomain crystal form 1, 2.3A

5NMT の概要

• エントリーDOI: 10.2210/pdb5nmt/pdb
• 分子名称: Sortilin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: vps10 domain, sorting receptor, dimer, acidic ph, transport protein
• 由来する生物種: Mus musculus (House mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 165591.67

構造登録者

Leloup, N.O.L.,Janssen, B.J.C. (登録日: 2017-04-07, 公開日: 2017-11-29, 最終更新日: 2024-11-20)

主引用文献

Leloup, N.,Lossl, P.,Meijer, D.H.,Brennich, M.,Heck, A.J.R.,Thies-Weesie, D.M.E.,Janssen, B.J.C.
Low pH-induced conformational change and dimerization of sortilin triggers endocytosed ligand release.
Nat Commun, 8:1708-1708, 2017

PubMed Abstract: Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a β-propeller containing endocytosis receptor, internalizes a diverse set of ligands with roles in cell differentiation and homeostasis. The molecular mechanisms of pH-mediated ligand release and sortilin recycling are unresolved. Here we present crystal structures that show the sortilin luminal segment (s-sortilin) undergoes a conformational change and dimerizes at low pH. The conformational change, within all three sortilin luminal domains, provides an altered surface and the dimers sterically shield a large interface while bringing the two s-sortilin C-termini into close proximity. Biophysical and cell-based assays show that members of two different ligand families, (pro)neurotrophins and neurotensin, preferentially bind the sortilin monomer. This indicates that sortilin dimerization and conformational change discharges ligands and triggers recycling. More generally, this work may reveal a double mechanism for low pH-induced ligand release by endocytosis receptors.

PubMed: 29167428
DOI: 10.1038/s41467-017-01485-5

実験手法

X-RAY DIFFRACTION (2.3 Å)