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TitleCalcium-dependent oligomerization of scavenger receptor CD163 facilitates the endocytosis of ligands.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 6679, Year 2025
Publish dateJul 21, 2025
AuthorsHua Xu / Xiaohui Song / Xiao-Dong Su /
PubMed AbstractScavenger 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 ...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.
External linksNat Commun / PubMed:40691148 / PubMed Central
MethodsEM (single particle)
Resolution2.94 - 3.21 Å
Structure data

38480

8xmk

EMDB-38480, PDB-8xmk:
Local refinement of SRCR5-9 domains
Method: EM (single particle) / Resolution: 3.03 Å

38485

8xmp

EMDB-38485, PDB-8xmp:
Structure of CD163 in complex with Hb-Hp
Method: EM (single particle) / Resolution: 3.11 Å

38486

8xmq

EMDB-38486, PDB-8xmq:
Structure of dimeric CD163 in complex with Hb-Hp
Method: EM (single particle) / Resolution: 3.21 Å

38490

8xmw

EMDB-38490, PDB-8xmw:
Local refinement of Hb-Hp bind to CD163
Method: EM (single particle) / Resolution: 2.94 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-CA:
Unknown entry

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE

Source
  • homo sapiens (human)
KeywordsENDOCYTOSIS / Homotrimer / receptor / scavenger receptor / ligand binding / EXOCYTOSIS

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