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Yorodumi- EMDB-49213: Composite map of the autoinhibitory unliganded CD163 trimer (map F) -
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Open data
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Basic information
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| Title | Composite map of the autoinhibitory unliganded CD163 trimer (map F) | |||||||||
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Sample |
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Keywords | CD163 / M130 / Scavenger receptor / ENDOCYTOSIS | |||||||||
| Function / homology | Function and homology informationCD163 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 | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Huang C-S / White JBR / Degtjarik O | |||||||||
| Funding support | United Kingdom, 2 items
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Citation | Journal: PLoS Biol / Year: 2025Title: Structural elucidation of the haptoglobin-hemoglobin clearance mechanism by macrophage scavenger receptor CD163. Authors: Ching-Shin Huang / Hui Wang / Joshua B R White / Oksana Degtjarik / Cindy Huynh / Kristoffer Brannstrom / Mark T Horn / Stephen P Muench / William S Somers / Javier Chaparro-Riggers / Laura ...Authors: Ching-Shin Huang / Hui Wang / Joshua B R White / Oksana Degtjarik / Cindy Huynh / Kristoffer Brannstrom / Mark T Horn / Stephen P Muench / William S Somers / Javier Chaparro-Riggers / Laura Lin / Lidia Mosyak / ![]() Abstract: Intravascular hemolysis releases hemoglobin into the bloodstream, which can damage vascular and renal tissues due to its oxidative nature. Circulating haptoglobin acts as a primary defense by binding ...Intravascular hemolysis releases hemoglobin into the bloodstream, which can damage vascular and renal tissues due to its oxidative nature. Circulating haptoglobin acts as a primary defense by binding to free hemoglobin, forming a haptoglobin-hemoglobin (HpHb) complex that is then recognized and cleared by the CD163 scavenger receptor on macrophages. While the function and structure of HpHb complex are mostly well-defined, the molecular mechanism underlying its interaction with CD163 remains unclear. Here we report the cryo-electron microscopy structures of human CD163 in its unliganded state and in its complex with HpHb. These structures reveal that CD163 functions as a trimer, forming a composite binding site at its center for one protomer of the dimeric HpHb, resulting in a 3:1 binding stoichiometry. In the unliganded state, CD163 can also form a trimer, but in an autoinhibitory configuration that occludes the ligand binding site. Widespread electrostatic interactions mediated by calcium ions are pivotal in both pre-ligand and ligand-bound receptor assemblies. This calcium-dependent mechanism enables CD163/HpHb complexes to assemble and, once internalized, disassemble into individual components upon reaching the endosome, where low calcium and lower pH conditions prevail. Collectively, this study elucidates the molecular mechanism by which CD163-mediated endocytosis efficiently clears different isoforms of HpHb. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_49213.map.gz | 129.8 MB | EMDB map data format | |
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| Header (meta data) | emd-49213-v30.xml emd-49213.xml | 17.3 KB 17.3 KB | Display Display | EMDB header |
| Images | emd_49213.png | 73.3 KB | ||
| Filedesc metadata | emd-49213.cif.gz | 6.7 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-49213 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-49213 | HTTPS FTP |
-Validation report
| Summary document | emd_49213_validation.pdf.gz | 466.4 KB | Display | EMDB validaton report |
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| Full document | emd_49213_full_validation.pdf.gz | 465.9 KB | Display | |
| Data in XML | emd_49213_validation.xml.gz | 6.9 KB | Display | |
| Data in CIF | emd_49213_validation.cif.gz | 8 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-49213 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-49213 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9nb5MC ![]() 9nb6C ![]() 9nb8C C: citing same article ( M: atomic model generated by this map |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_49213.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.11 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : CD163 trimer
| Entire | Name: CD163 trimer |
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| Components |
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-Supramolecule #1: CD163 trimer
| Supramolecule | Name: CD163 trimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 400 KDa |
-Macromolecule #1: Scavenger receptor cysteine-rich type 1 protein M130
| Macromolecule | Name: Scavenger receptor cysteine-rich type 1 protein M130 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 109.731555 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: 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 ATTGRSHHHH HHHH UniProtKB: Scavenger receptor cysteine-rich type 1 protein M130 |
-Macromolecule #2: CALCIUM ION
| Macromolecule | Name: CALCIUM ION / type: ligand / ID: 2 / Number of copies: 20 / Formula: CA |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
| Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 9 / Formula: NAG |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 221.208 Da |
| Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 0.1 mg/mL |
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| Buffer | pH: 7.5 |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Specialist optics | Energy filter - Name: TFS Selectris / Energy filter - Slit width: 10 eV |
| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.67 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
| Initial model | Chain - Source name: AlphaFold / Chain - Initial model type: in silico model |
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| Refinement | Space: REAL / Protocol: AB INITIO MODEL / Overall B value: 70.7 |
| Output model | ![]() PDB-9nb5: |
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About Yorodumi



Keywords
Homo sapiens (human)
Authors
United Kingdom, 2 items
Citation



























Z (Sec.)
Y (Row.)
X (Col.)





















FIELD EMISSION GUN
