7ZEU

Crystal structure of human Clusterin, crystal form II

7ZEU の概要

• エントリーDOI: 10.2210/pdb7zeu/pdb
• 分子名称: Clusterin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: molecular chaperone, complement system, alzheimer's disease, chaperone
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97748.17

構造登録者

Yuste-Checa, P.,Bracher, A.,Hartl, F.U. (登録日: 2022-03-31, 公開日: 2023-10-11, 最終更新日: 2026-03-04)

主引用文献

Yuste-Checa, P.,Carvajal, A.I.,Mi, C.,Paatz, S.,Hartl, F.U.,Bracher, A.
Structural analyses define the molecular basis of clusterin chaperone function.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Clusterin (apolipoprotein J), a conserved glycoprotein abundant in blood and cerebrospinal fluid, functions as a molecular chaperone and apolipoprotein. Dysregulation of clusterin is linked to late-onset Alzheimer disease. Despite its prominent role in extracellular proteostasis, the mechanism of clusterin function remained unclear. Here, we present crystal structures of human clusterin, revealing a discontinuous three-domain architecture. Structure-based mutational analysis demonstrated that two disordered, hydrophobic peptide tails enable diverse activities. Resembling the substrate-binding regions of small heat-shock proteins, these sequences mediate clusterin's chaperone function in suppressing amyloid-β, tau and α-synuclein aggregation. In conjunction with conserved surface areas, the tail segments also participate in clusterin binding to cell surface receptors and cellular uptake. While contributing to lipoprotein formation, the hydrophobic tails remain accessible for chaperone function in the lipoprotein complex. The remarkable versatility of these sequences allows clusterin to function alone or bound to lipids in maintaining the solubility of aberrant extracellular proteins and facilitating their clearance by endocytosis and lysosomal degradation.

PubMed: 40781479
DOI: 10.1038/s41594-025-01631-4

実験手法

X-RAY DIFFRACTION (3.5 Å)