6EHO

Dimer of the Sortilin Vps10p domain at low pH

6EHO の概要

• エントリーDOI: 10.2210/pdb6eho/pdb
• 分子名称: Sortilin, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-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, ... (4 entities in total)
• 機能のキーワード: protein sorting receptor, 10-bladed beta-propeller, vps10p-d, endocytosis, endosome, glycoprotein, golgi apparatus, lysosome, membrane, receptor, transmembrane, signaling protein, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 82302.56

構造登録者

Thirup, S.S.,Quistgaard, E.H.,Januliene, D.,Andersen, J.L.,Nielsen, J.A. (登録日: 2017-09-14, 公開日: 2017-12-06, 最終更新日: 2024-11-06)

主引用文献

Januliene, D.,Andersen, J.L.,Nielsen, J.A.,Quistgaard, E.M.,Hansen, M.,Strandbygaard, D.,Moeller, A.,Petersen, C.M.,Madsen, P.,Thirup, S.S.
Acidic Environment Induces Dimerization and Ligand Binding Site Collapse in the Vps10p Domain of Sortilin.
Structure, 25:1809-1819.e3, 2017

PubMed Abstract: Sortilin is a neuronal receptor involved in transmembrane signaling, endocytosis, and intracellular sorting of proteins. It cycles through a number of cellular compartments where it encounters various acidic conditions. The crystal structure of the sortilin ectodomain has previously been determined at neutral pH. Here, we present the 3.5-Å resolution crystal structure of sortilin at pH 5.5, which represents an environment similar to that of late endosomes, where ligands are released. The structure reveals an overall distortion of the 10-bladed β-propeller domain. This distortion and specific conformational changes, caused by protonation of a number of histidine residues, render the currently known binding sites unavailable for ligand binding. Access to the binding sites is furthermore blocked by a reversible and pH-dependent formation of tight sortilin dimers, also confirmed by electron microscopy, size-exclusion chromatography, and mutational studies. This study reveals how sortilin binding sites are disrupted and explains pH-dependent ligand affinity.

PubMed: 29107483
DOI: 10.1016/j.str.2017.09.015

実験手法

X-RAY DIFFRACTION (3.5 Å)