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- EMDB-52078: Dimeric CD163 bound to human haptoglobin-haemoglobin complex -

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Basic information

Entry
Database: EMDB / ID: EMD-52078
TitleDimeric CD163 bound to human haptoglobin-haemoglobin complex
Map dataDeep EMhancer-sharpened map
Sample
  • Complex: CD163:HpHb complex
    • Protein or peptide: Scavenger receptor cysteine-rich type 1 protein M130
    • Protein or peptide: Hemoglobin subunit alpha
    • Protein or peptide: Hemoglobin subunit beta
    • Protein or peptide: Isoform 2 of Haptoglobin
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: PROTOPORPHYRIN IX CONTAINING FE
  • Ligand: OXYGEN MOLECULE
KeywordsCD163 / haptoglobin-haemoglobin complex / haemoglobin detoxification / ligand uptake / scavenger receptor / SRCR domain-containing protein / 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 / renal absorption / haptoglobin-hemoglobin complex ...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 / renal absorption / haptoglobin-hemoglobin complex / hemoglobin complex / antioxidant activity / oxygen transport / Scavenging of heme from plasma / immune system process / endocytic vesicle lumen / blood vessel diameter maintenance / acute-phase response / Late endosomal microautophagy / 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 / defense response / Cytoprotection by HMOX1 / oxygen binding / Chaperone Mediated Autophagy / regulation of blood pressure / platelet aggregation / specific granule lumen / endocytic vesicle membrane / positive regulation of nitric oxide biosynthetic process / 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 / inflammatory response / iron ion binding / serine-type endopeptidase activity / external side of plasma membrane / 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: 2.82 Å
AuthorsZhou RX / Higgins MK
Funding support United Kingdom, 2 items
OrganizationGrant numberCountry
Wellcome Trust218482/Z/19/Z United Kingdom
Wellcome Trust220797/Z/20/Z United Kingdom
CitationJournal: Nat Commun / Year: 2025
Title: Scavenger receptor CD163 multimerises to allow uptake of diverse ligands.
Authors: Richard X Zhou / Matthew K Higgins /
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 ...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.
History
DepositionNov 14, 2024-
Header (metadata) releaseJul 2, 2025-
Map releaseJul 2, 2025-
UpdateJul 30, 2025-
Current statusJul 30, 2025Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_52078.png

Downloads & links

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Map

FileDownload / File: emd_52078.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationDeep EMhancer-sharpened map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 512 pix.
= 425.984 Å		0.83 Å/pix.
x 512 pix.
= 425.984 Å		0.83 Å/pix.
x 512 pix.
= 425.984 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.832 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.08
Minimum - Maximum-0.0018110796 - 1.8317379
Average (Standard dev.)0.00038716214 (±0.013562876)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 425.984 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: unsharpened map

Fileemd_52078_additional_1.map
Annotationunsharpened map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_52078_half_map_1.map
Annotationhalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map A

Fileemd_52078_half_map_2.map
Annotationhalf map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : CD163:HpHb complex

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

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Supramolecule #1: CD163:HpHb complex

SupramoleculeName: CD163:HpHb complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)

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

MacromoleculeName: Scavenger receptor cysteine-rich type 1 protein M130 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 125.594805 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MSKLRMVLLE DSGSADFRRH FVNLSPFTIT VVLLLSACFV TSSLGGTDKE LRLVDGENKC SGRVEVKVQE EWGTVCNNGW SMEAVSVIC NQLGCPTAIK APGWANSSAG SGRIWMDHVS CRGNESALWD CKHDGWGKHS NCTHQQDAGV TCSDGSNLEM R LTRGGNMC ...String:
MSKLRMVLLE DSGSADFRRH FVNLSPFTIT VVLLLSACFV TSSLGGTDKE LRLVDGENKC SGRVEVKVQE EWGTVCNNGW SMEAVSVIC NQLGCPTAIK APGWANSSAG SGRIWMDHVS CRGNESALWD CKHDGWGKHS NCTHQQDAGV TCSDGSNLEM R LTRGGNMC SGRIEIKFQG RWGTVCDDNF NIDHASVICR QLECGSAVSF SGSSNFGEGS GPIWFDDLIC NGNESALWNC KH QGWGKHN CDHAEDAGVI CSKGADLSLR LVDGVTECSG RLEVRFQGEW GTICDDGWDS YDAAVACKQL GCPTAVTAIG RVN ASKGFG HIWLDSVSCQ GHEPAIWQCK HHEWGKHYCN HNEDAGVTCS DGSDLELRLR GGGSRCAGTV EVEIQRLLGK VCDR GWGLK EADVVCRQLG CGSALKTSYQ VYSKIQATNT WLFLSSCNGN ETSLWDCKNW QWGGLTCDHY EEAKITCSAH REPRL VGGD IPCSGRVEVK HGDTWGSICD SDFSLEAASV LCRELQCGTV VSILGGAHFG EGNGQIWAEE FQCEGHESHL SLCPVA PRP EGTCSHSRDV GVVCSRYTEI RLVNGKTPCE GRVELKTLGA WGSLCNSHWD IEDAHVLCQQ LKCGVALSTP GGARFGK GN GQIWRHMFHC TGTEQHMGDC PVTALGASLC PSEQVASVIC SGNQSQTLSS CNSSSLGPTR PTIPEESAVA CIESGQLR L VNGGGRCAGR VEIYHEGSWG TICDDSWDLS DAHVVCRQLG CGEAINATGS AHFGEGTGPI WLDEMKCNGK ESRIWQCHS HGWGQQNCRH KEDAGVICSE FMSLRLTSEA SREACAGRLE VFYNGAWGTV GKSSMSETTV GVVCRQLGCA DKGKINPASL DKAMSIPMW VDNVQCPKGP DTLWQCPSSP WEKRLASPSE ETWITCDNKI RLQEGPTSCS GRVEIWHGGS WGTVCDDSWD L DDAQVVCQ QLGCGPALKA FKEAEFGQGT GPIWLNEVKC KGNESSLWDC PARRWGHSEC GHKEDAAVNC TDISVQKTPQ KA TTGRSSR QSSFIAVGIL GVVLLAIFVA LFFLTKKRRQ RQRLAVSSRG ENLVHQIQYR EMNSCLNADD LDLMNSSENS HES ADFSAA ELISVSKFLP ISGMEKEAIL SHTEKENGNL

UniProtKB: Scavenger receptor cysteine-rich type 1 protein M130

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Macromolecule #2: Hemoglobin subunit alpha

MacromoleculeName: Hemoglobin subunit alpha / type: protein_or_peptide / ID: 2 / 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 #3: Hemoglobin subunit beta

MacromoleculeName: Hemoglobin subunit beta / type: protein_or_peptide / ID: 3 / 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 #4: Isoform 2 of Haptoglobin

MacromoleculeName: Isoform 2 of Haptoglobin / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 38.497652 KDa
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 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 4 / 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: 9 / 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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Macromolecule #9: OXYGEN MOLECULE

MacromoleculeName: OXYGEN MOLECULE / type: ligand / ID: 9 / Number of copies: 2 / Formula: OXY
Molecular weightTheoretical: 31.999 Da
Chemical component information

ChemComp-O2:
OXYGEN MOLECULE

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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: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 41.68 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: 0.4 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: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.82 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 456124
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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