3WSY

SorLA Vps10p domain in complex with its own propeptide fragment

3WSY の概要

• エントリーDOI: 10.2210/pdb3wsy/pdb
• 関連するPDBエントリー: 3WSX 3WSZ
• 分子名称: Sortilin-related receptor, peptide from Sortilin-related receptor, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: beta-propeller, receptor, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79373.73

構造登録者

Kitago, Y.,Nakata, Z.,Nagae, M.,Nogi, T.,Takagi, J. (登録日: 2014-03-30, 公開日: 2015-02-04, 最終更新日: 2024-10-30)

主引用文献

Kitago, Y.,Nagae, M.,Nakata, Z.,Yagi-Utsumi, M.,Takagi-Niidome, S.,Mihara, E.,Nogi, T.,Kato, K.,Takagi, J.
Structural basis for amyloidogenic peptide recognition by sorLA.
Nat.Struct.Mol.Biol., 22:199-206, 2015

PubMed Abstract: SorLA is a neuronal sorting receptor considered to be a major risk factor for Alzheimer's disease. We have recently reported that it directs lysosomal targeting of nascent neurotoxic amyloid-β (Aβ) peptides by directly binding Aβ. Here, we determined the crystal structure of the human sorLA domain responsible for Aβ capture, Vps10p, in an unbound state and in complex with two ligands. Vps10p assumes a ten-bladed β-propeller fold with a large tunnel at the center. An internal ligand derived from the sorLA propeptide bound inside the tunnel to extend the β-sheet of one of the propeller blades. The structure of the sorLA Vps10p-Aβ complex revealed that the same site is used. Peptides are recognized by sorLA Vps10p in redundant modes without strict dependence on a particular amino acid sequence, thus suggesting a broad specificity toward peptides with a propensity for β-sheet formation.

PubMed: 25643321
DOI: 10.1038/nsmb.2954

実験手法

X-RAY DIFFRACTION (3.11 Å)