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- EMDB-38480: Local refinement of SRCR5-9 domains -

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Basic information

Entry
Database: EMDB / ID: EMD-38480
TitleLocal refinement of SRCR5-9 domains
Map data
Sample
  • Complex: CD163 homotrimer
    • Protein or peptide: Scavenger receptor cysteine-rich type 1 protein M130
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
KeywordsHomotrimer / receptor / ENDOCYTOSIS
Function / homology
Function and homology information


CD163 mediating an anti-inflammatory response / scavenger receptor activity / Scavenging of heme from plasma / acute-phase response / endocytic vesicle membrane / scaffold protein binding / external side of plasma membrane / extracellular region / 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
Similarity search - Domain/homology
Scavenger receptor cysteine-rich type 1 protein M130
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.03 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_38480.png

Downloads & links

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Map

FileDownload / File: emd_38480.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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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

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.07 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-2.4262106 - 2.9042306
Average (Standard dev.)0.00053924654 (±0.043834303)
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: #2

Fileemd_38480_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: #1

Fileemd_38480_half_map_2.map
Projections & Slices
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Histogram

Histogram (log scale)

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Sample components

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Entire : CD163 homotrimer

EntireName: CD163 homotrimer
Components
  • Complex: CD163 homotrimer
    • Protein or peptide: Scavenger receptor cysteine-rich type 1 protein M130
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION

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Supramolecule #1: CD163 homotrimer

SupramoleculeName: CD163 homotrimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
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: 3 / 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 #2: 2-acetamido-2-deoxy-beta-D-glucopyranose

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

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

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Macromolecule #3: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 3 / Number of copies: 17 / Formula: CA
Molecular weightTheoretical: 40.078 Da

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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: 3.03 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 432933
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

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