9NB5

Cryo-EM structure of the autoinhibitory CD163 trimer

9NB5 の概要

• エントリーDOI: 10.2210/pdb9nb5/pdb
• EMDBエントリー: 49213
• 分子名称: Scavenger receptor cysteine-rich type 1 protein M130, CALCIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: cd163, m130, scavenger receptor, endocytosis
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 331987.10

構造登録者

Huang, C.-S.,White, J.B.R.,Degtjarik, O.,Mosyak, L. (登録日: 2025-02-13, 公開日: 2025-06-18, 最終更新日: 2025-07-23)

主引用文献

Huang, C.S.,Wang, H.,White, J.B.R.,Degtjarik, O.,Huynh, C.,Brannstrom, K.,Horn, M.T.,Muench, S.P.,Somers, W.S.,Chaparro-Riggers, J.,Lin, L.,Mosyak, L.
Structural elucidation of the haptoglobin-hemoglobin clearance mechanism by macrophage scavenger receptor CD163.
Plos Biol., 23:e3003264-e3003264, 2025

PubMed Abstract: Intravascular hemolysis releases hemoglobin into the bloodstream, which can damage vascular and renal tissues due to its oxidative nature. Circulating haptoglobin acts as a primary defense by binding to free hemoglobin, forming a haptoglobin-hemoglobin (HpHb) complex that is then recognized and cleared by the CD163 scavenger receptor on macrophages. While the function and structure of HpHb complex are mostly well-defined, the molecular mechanism underlying its interaction with CD163 remains unclear. Here we report the cryo-electron microscopy structures of human CD163 in its unliganded state and in its complex with HpHb. These structures reveal that CD163 functions as a trimer, forming a composite binding site at its center for one protomer of the dimeric HpHb, resulting in a 3:1 binding stoichiometry. In the unliganded state, CD163 can also form a trimer, but in an autoinhibitory configuration that occludes the ligand binding site. Widespread electrostatic interactions mediated by calcium ions are pivotal in both pre-ligand and ligand-bound receptor assemblies. This calcium-dependent mechanism enables CD163/HpHb complexes to assemble and, once internalized, disassemble into individual components upon reaching the endosome, where low calcium and lower pH conditions prevail. Collectively, this study elucidates the molecular mechanism by which CD163-mediated endocytosis efficiently clears different isoforms of HpHb.

PubMed: 40644526
DOI: 10.1371/journal.pbio.3003264

実験手法

ELECTRON MICROSCOPY (3 Å)