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- PDB-8xmq: Structure of dimeric CD163 in complex with Hb-Hp -

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Basic information

Entry
Database: PDB / ID: 8xmq
TitleStructure of dimeric CD163 in complex with Hb-Hp
Components
  • (Hemoglobin subunit ...) x 2
  • Isoform 2 of Haptoglobin
  • Scavenger receptor cysteine-rich type 1 protein M130
KeywordsENDOCYTOSIS / scavenger receptor / ligand binding
Function / homology
Function and homology information


negative regulation of hydrogen peroxide catabolic process / zymogen activation / CD163 mediating an anti-inflammatory response / scavenger receptor activity / nitric oxide transport / hemoglobin alpha binding / cellular oxidant detoxification / hemoglobin binding / haptoglobin-hemoglobin complex / renal absorption ...negative regulation of hydrogen peroxide catabolic process / zymogen activation / CD163 mediating an anti-inflammatory response / scavenger receptor activity / nitric oxide transport / hemoglobin alpha binding / cellular oxidant detoxification / hemoglobin binding / haptoglobin-hemoglobin complex / renal absorption / hemoglobin complex / antioxidant activity / oxygen transport / immune system process / Scavenging of heme from plasma / endocytic vesicle lumen / blood vessel diameter maintenance / acute-phase response / hydrogen peroxide catabolic process / oxygen carrier activity / carbon dioxide transport / response to hydrogen peroxide / Heme signaling / Erythrocytes take up oxygen and release carbon dioxide / Erythrocytes take up carbon dioxide and release oxygen / Late endosomal microautophagy / defense response / Cytoprotection by HMOX1 / oxygen binding / regulation of blood pressure / platelet aggregation / specific granule lumen / Chaperone Mediated Autophagy / positive regulation of nitric oxide biosynthetic process / endocytic vesicle membrane / tertiary granule lumen / Factors involved in megakaryocyte development and platelet production / scaffold protein binding / blood microparticle / ficolin-1-rich granule lumen / defense response to bacterium / iron ion binding / inflammatory response / external side of plasma membrane / serine-type endopeptidase activity / heme binding / Neutrophil degranulation / extracellular space / extracellular exosome / extracellular region / metal ion binding / membrane / plasma membrane / cytosol
Similarity search - Function
SRCR domain signature. / Scavenger receptor cysteine-rich domain / SRCR domain profile. / SRCR-like domain superfamily / Scavenger receptor Cys-rich / SRCR domain / Sushi/SCR/CCP domain / Sushi/CCP/SCR domain profile. / Sushi/SCR/CCP superfamily / Hemoglobin, pi ...SRCR domain signature. / Scavenger receptor cysteine-rich domain / SRCR domain profile. / SRCR-like domain superfamily / Scavenger receptor Cys-rich / SRCR domain / Sushi/SCR/CCP domain / Sushi/CCP/SCR domain profile. / Sushi/SCR/CCP superfamily / Hemoglobin, pi / Hemoglobin, alpha-type / Hemoglobin, beta-type / : / Globin/Protoglobin / Globin / Globin / Globin domain profile. / Globin-like superfamily / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin domain profile. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan
Similarity search - Domain/homology
PROTOPORPHYRIN IX CONTAINING FE / Haptoglobin / Hemoglobin subunit beta / Hemoglobin subunit alpha / Scavenger receptor cysteine-rich type 1 protein M130
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.21 Å
AuthorsXu, H. / Su, X.D.
Funding support China, 1items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2021YFC2301400 China
CitationJournal: Nat Commun / Year: 2025
Title: Calcium-dependent oligomerization of scavenger receptor CD163 facilitates the endocytosis of ligands.
Authors: Hua Xu / Xiaohui Song / Xiao-Dong Su /
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 ...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.
History
DepositionDec 27, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jan 1, 2025Provider: repository / Type: Initial release
Revision 1.1Jul 30, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.pdbx_database_id_DOI / _citation.title / _citation.year / _em_admin.last_update
Revision 1.2Aug 6, 2025Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.page_last / _citation.pdbx_database_id_PubMed ..._citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
2: Isoform 2 of Haptoglobin
F: Scavenger receptor cysteine-rich type 1 protein M130
D: Scavenger receptor cysteine-rich type 1 protein M130
C: Hemoglobin subunit alpha
G: Hemoglobin subunit beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)292,25828
Polymers288,1465
Non-polymers4,11123
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 2 types, 3 molecules 2FD

#1: Protein Isoform 2 of Haptoglobin / Zonulin


Mass: 38497.652 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HP / Production host: Homo sapiens (human) / References: UniProt: P00738
#2: Protein Scavenger receptor cysteine-rich type 1 protein M130 / Hemoglobin scavenger receptor


Mass: 109172.922 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CD163, M130 / Production host: Homo sapiens (human) / References: UniProt: Q86VB7

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Hemoglobin subunit ... , 2 types, 2 molecules CG

#3: Protein Hemoglobin subunit alpha / Alpha-globin / Hemoglobin alpha chain


Mass: 15281.550 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P69905
#4: Protein Hemoglobin subunit beta / Beta-globin / Hemoglobin beta chain


Mass: 16021.396 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P68871

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Sugars , 2 types, 9 molecules

#5: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#6: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Non-polymers , 2 types, 14 molecules

#7: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: Ca
#8: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME


Mass: 616.487 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H32FeN4O4

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Details

Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Dimeric CD163 in complex with Hb-Hp / Type: COMPLEX / Entity ID: #1, #3, #2, #4 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.2
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.21 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 332640 / Symmetry type: POINT

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