9TQD

CD163 bound to haemoglobin

This is a non-PDB format compatible entry.

Summary for 9TQD

• Entry DOI: 10.2210/pdb9tqd/pdb
• EMDB information: 56135
• Descriptor: Scavenger receptor cysteine-rich type 1 protein M130, Hemopressin, Spinorphin, ... (8 entities in total)
• Functional Keywords: cd163, haemoglobin, haptoglobin-haemoglobin receptor, cell adhesion
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 446517.17

Authors

Zhou, R.X.,Higgins, M.K. (deposition date: 2025-12-20, release date: 2026-04-15, Last modification date: 2026-05-27)

Primary citation

Zhou, R.X.,Higgins, M.K.
Structural basis for hemoglobin scavenging by CD163 reveals mechanism of ligand promiscuity.
Plos Biol., 24:e3003788-e3003788, 2026

PubMed Abstract: The scavenger receptor CD163 detoxifies free hemoglobin released on erythrocyte lysis to prevent oxidative damage. The best understood route for hemoglobin detoxification involves the formation of haptoglobin-hemoglobin complexes that bind CD163 and are internalized into macrophages, resulting in hemoglobin degradation. However, during conditions such as sickle cell anemia or malaria, haptoglobin is depleted. CD163 can then act as a lower-affinity receptor for free hemoglobin. Previous studies revealed that CD163 forms a multimeric "base," which presents "arms" that form a binding site for haptoglobin-hemoglobin. In this study, we use cryogenic electron microscopy to reveal how human CD163 binds hemoglobin tetramers in a process that, unlike haptoglobin-hemoglobin uptake, requires a full trimeric CD163 assembly to achieve sufficient binding. We reveal how flexibility at the calcium-mediated base, combined with a hinge between receptor domains 2 and 3, allows the arms to wrap around diverse ligands. This brings together multiple small binding surfaces from different domains to form cradles for different ligands. These adaptations allow the scavenger receptor to be promiscuous, protecting us from oxidative damage caused by hemoglobin release in various pathological conditions.

PubMed: 42133656
DOI: 10.1371/journal.pbio.3003788

Experimental method

ELECTRON MICROSCOPY (2.8 Å)