9HEK

Trimeric CD163 bound to human haptoglobin-haemoglobin complex

Summary for 9HEK

• Entry DOI: 10.2210/pdb9hek/pdb
• EMDB information: 52079
• Descriptor: Scavenger receptor cysteine-rich type 1 protein M130, OXYGEN MOLECULE, Hemoglobin subunit alpha, ... (10 entities in total)
• Functional Keywords: cd163, haptoglobin-haemoglobin complex, haemoglobin detoxification, ligand uptake, scavenger receptor, srcr domain-containing protein, endocytosis
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 452254.86

Authors

Zhou, R.X.,Higgins, M.K. (deposition date: 2024-11-14, release date: 2025-07-02, Last modification date: 2025-07-30)

Primary citation

Zhou, R.X.,Higgins, M.K.
Scavenger receptor CD163 multimerises to allow uptake of diverse ligands.
Nat Commun, 16:6623-6623, 2025

PubMed Abstract: CD163 is an archetypal scavenger receptor and mediates detoxification of free haemoglobin. Release of haemoglobin from lysed erythrocytes causes oxidative tissue and organ damage. Detoxification involves haemoglobin binding to the abundant serum protein haptoglobin, followed by CD163-mediated uptake of stoichiometrically diverse haptoglobin-haemoglobin complexes into macrophages for degradation. We show that CD163 adopts dimeric and trimeric assemblies due to calcium-mediated interactions within a membrane-associated base. Arms protrude from this base and create a ligand-binding site. Flexibility within the base, coupled with multiple small ligand-binding surfaces on each arm, allow the receptor to mould around its ligands, resulting in promiscuous uptake of ligands with different structures and stoichiometries. Monomeric CD163 lacks this ability to internalise lower-avidity ligands. Arms from adjacent protomers can also self-associate, blocking ligand-binding surfaces in an autoinhibited state. Therefore, through calcium-dependent multimer formation and flexible ligand binding, CD163 scavenges ligands with different structures and avidities, mediating haemoglobin detoxification.

PubMed: 40681524
DOI: 10.1038/s41467-025-62054-9

Experimental method

ELECTRON MICROSCOPY (3.15 Å)