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- EMDB-38486: Structure of dimeric CD163 in complex with Hb-Hp -

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Basic information

Entry
Database: EMDB / ID: EMD-38486
TitleStructure of dimeric CD163 in complex with Hb-Hp
Map data
Sample
  • Complex: Dimeric CD163 in complex with Hb-Hp
    • Protein or peptide: Isoform 2 of Haptoglobin
    • Protein or peptide: Hemoglobin subunit alpha
    • Protein or peptide: Scavenger receptor cysteine-rich type 1 protein M130
    • Protein or peptide: Hemoglobin subunit beta
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: PROTOPORPHYRIN IX CONTAINING FE
Keywordsscavenger receptor / ligand binding / ENDOCYTOSIS
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
Haptoglobin / Hemoglobin subunit beta / Hemoglobin subunit alpha / Scavenger receptor cysteine-rich type 1 protein M130
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.21 Å
AuthorsXu H / Su XD
Funding support China, 1 items
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, 2023-
Header (metadata) releaseJan 1, 2025-
Map releaseJan 1, 2025-
UpdateAug 6, 2025-
Current statusAug 6, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_38486.png

Downloads & links

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Map

FileDownload / File: emd_38486.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 360 pix.
= 385.2 Å		1.07 Å/pix.
x 360 pix.
= 385.2 Å		1.07 Å/pix.
x 360 pix.
= 385.2 Å

Surface

Projections

Slices (1/3)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.07 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-2.1320693 - 2.722154
Average (Standard dev.)0.00027048448 (±0.033829883)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 385.2 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_38486_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_38486_half_map_2.map
Projections & Slices
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Histogram (log scale)

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Sample components

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Entire : Dimeric CD163 in complex with Hb-Hp

EntireName: Dimeric CD163 in complex with Hb-Hp
Components
  • Complex: Dimeric CD163 in complex with Hb-Hp
    • Protein or peptide: Isoform 2 of Haptoglobin
    • Protein or peptide: Hemoglobin subunit alpha
    • Protein or peptide: Scavenger receptor cysteine-rich type 1 protein M130
    • Protein or peptide: Hemoglobin subunit beta
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: PROTOPORPHYRIN IX CONTAINING FE

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Supramolecule #1: Dimeric CD163 in complex with Hb-Hp

SupramoleculeName: Dimeric CD163 in complex with Hb-Hp / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1, #3, #2, #4
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Isoform 2 of Haptoglobin

MacromoleculeName: Isoform 2 of Haptoglobin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 38.497652 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MSALGAVIAL LLWGQLFAVD SGNDVTDIAD DGCPKPPEIA HGYVEHSVRY QCKNYYKLRT EGDGVYTLNN EKQWINKAVG DKLPECEAV CGKPKNPANP VQRILGGHLD AKGSFPWQAK MVSHHNLTTG ATLINEQWLL TTAKNLFLNH SENATAKDIA P TLTLYVGK ...String:
MSALGAVIAL LLWGQLFAVD SGNDVTDIAD DGCPKPPEIA HGYVEHSVRY QCKNYYKLRT EGDGVYTLNN EKQWINKAVG DKLPECEAV CGKPKNPANP VQRILGGHLD AKGSFPWQAK MVSHHNLTTG ATLINEQWLL TTAKNLFLNH SENATAKDIA P TLTLYVGK KQLVEIEKVV LHPNYSQVDI GLIKLKQKVS VNERVMPICL PSKDYAEVGR VGYVSGWGRN ANFKFTDHLK YV MLPVADQ DQCIRHYEGS TVPEKKTPKS PVGVQPILNE HTFCAGMSKY QEDTCYGDAG SAFAVHDLEE DTWYATGILS FDK SCAVAE YGVYVKVTSI QDWVQKTIAE N

UniProtKB: Haptoglobin

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Macromolecule #2: Scavenger receptor cysteine-rich type 1 protein M130

MacromoleculeName: Scavenger receptor cysteine-rich type 1 protein M130 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 109.172922 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SSLGGTDKEL RLVDGENKCS GRVEVKVQEE WGTVCNNGWS MEAVSVICNQ LGCPTAIKAP GWANSSAGSG RIWMDHVSCR GNESALWDC KHDGWGKHSN CTHQQDAGVT CSDGSNLEMR LTRGGNMCSG RIEIKFQGRW GTVCDDNFNI DHASVICRQL E CGSAVSFS ...String:
SSLGGTDKEL RLVDGENKCS GRVEVKVQEE WGTVCNNGWS MEAVSVICNQ LGCPTAIKAP GWANSSAGSG RIWMDHVSCR GNESALWDC KHDGWGKHSN CTHQQDAGVT CSDGSNLEMR LTRGGNMCSG RIEIKFQGRW GTVCDDNFNI DHASVICRQL E CGSAVSFS GSSNFGEGSG PIWFDDLICN GNESALWNCK HQGWGKHNCD HAEDAGVICS KGADLSLRLV DGVTECSGRL EV RFQGEWG TICDDGWDSY DAAVACKQLG CPTAVTAIGR VNASKGFGHI WLDSVSCQGH EPAIWQCKHH EWGKHYCNHN EDA GVTCSD GSDLELRLRG GGSRCAGTVE VEIQRLLGKV CDRGWGLKEA DVVCRQLGCG SALKTSYQVY SKIQATNTWL FLSS CNGNE TSLWDCKNWQ WGGLTCDHYE EAKITCSAHR EPRLVGGDIP CSGRVEVKHG DTWGSICDSD FSLEAASVLC RELQC GTVV SILGGAHFGE GNGQIWAEEF QCEGHESHLS LCPVAPRPEG TCSHSRDVGV VCSRYTEIRL VNGKTPCEGR VELKTL GAW GSLCNSHWDI EDAHVLCQQL KCGVALSTPG GARFGKGNGQ IWRHMFHCTG TEQHMGDCPV TALGASLCPS EQVASVI CS GNQSQTLSSC NSSSLGPTRP TIPEESAVAC IESGQLRLVN GGGRCAGRVE IYHEGSWGTI CDDSWDLSDA HVVCRQLG C GEAINATGSA HFGEGTGPIW LDEMKCNGKE SRIWQCHSHG WGQQNCRHKE DAGVICSEFM SLRLTSEASR EACAGRLEV FYNGAWGTVG KSSMSETTVG VVCRQLGCAD KGKINPASLD KAMSIPMWVD NVQCPKGPDT LWQCPSSPWE KRLASPSEET WITCDNKIR LQEGPTSCSG RVEIWHGGSW GTVCDDSWDL DDAQVVCQQL GCGPALKAFK EAEFGQGTGP IWLNEVKCKG N ESSLWDCP ARRWGHSECG HKEDAAVNCT DISVQKTPQK ATTGRSSRQS S

UniProtKB: Scavenger receptor cysteine-rich type 1 protein M130

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Macromolecule #3: Hemoglobin subunit alpha

MacromoleculeName: Hemoglobin subunit alpha / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 15.28155 KDa
SequenceString:
MVLSPADKTN VKAAWGKVGA HAGEYGAEAL ERMFLSFPTT KTYFPHFDLS HGSAQVKGHG KKVADALTNA VAHVDDMPNA LSALSDLHA HKLRVDPVNF KLLSHCLLVT LAAHLPAEFT PAVHASLDKF LASVSTVLTS KYR

UniProtKB: Hemoglobin subunit alpha

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Macromolecule #4: Hemoglobin subunit beta

MacromoleculeName: Hemoglobin subunit beta / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 16.021396 KDa
SequenceString:
MVHLTPEEKS AVTALWGKVN VDEVGGEALG RLLVVYPWTQ RFFESFGDLS TPDAVMGNPK VKAHGKKVLG AFSDGLAHLD NLKGTFATL SELHCDKLHV DPENFRLLGN VLVCVLAHHF GKEFTPPVQA AYQKVVAGVA NALAHKYH

UniProtKB: Hemoglobin subunit beta

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Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 7 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

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Macromolecule #7: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 7 / Number of copies: 12 / Formula: CA
Molecular weightTheoretical: 40.078 Da

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Macromolecule #8: PROTOPORPHYRIN IX CONTAINING FE

MacromoleculeName: PROTOPORPHYRIN IX CONTAINING FE / type: ligand / ID: 8 / Number of copies: 2 / Formula: HEM
Molecular weightTheoretical: 616.487 Da
Chemical component information

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.2
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.21 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 332640
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

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