8XMP

Structure of CD163 in complex with Hb-Hp

8XMP の概要

• エントリーDOI: 10.2210/pdb8xmp/pdb
• EMDBエントリー: 38485
• 分子名称: Isoform 2 of Haptoglobin, Scavenger receptor cysteine-rich type 1 protein M130, Hemoglobin subunit alpha, ... (8 entities in total)
• 機能のキーワード: scavenger receptor, ligand binding, endocytosis
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 402959.41

構造登録者

Xu, H.,Su, X.D. (登録日: 2023-12-27, 公開日: 2025-01-01, 最終更新日: 2025-08-06)

主引用文献

Xu, H.,Song, X.,Su, X.D.
Calcium-dependent oligomerization of scavenger receptor CD163 facilitates the endocytosis of ligands.
Nat Commun, 16:6679-6679, 2025

PubMed Abstract: Scavenger receptor CD163 is a marker of M2 type macrophages that play important roles in anti-inflammatory processes. The most extensively studied function of CD163 is related to the elimination of hemoglobin-haptoglobin (Hb-Hp) complexes, to prevent potential oxidative toxicity of the iron-containing heme. However, the structural mechanism of CD163 in ligand binding and internalization remains elusive. Here, we present the cryo-electron microscopy structure of human Hb-Hp recognition by the full ectodomain of CD163. We illuminate that CD163 forms calcium-dependent oligomers and primarily exists as trimeric form under the condition of 2.5 mM calcium. It mainly utilizes two protomers to interact with Hb-Hp complex asymmetrically, while the third protomer of the trimer also has the potential to form calcium-mediated contacts with Hp. Flow cytometry analyses reveal that oligomerization of CD163 significantly enhances the efficiency of ligand endocytosis. These results advance our understanding of the role of CD163 in ligand scavenging.

PubMed: 40691148
DOI: 10.1038/s41467-025-62013-4

実験手法

ELECTRON MICROSCOPY (3.11 Å)