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- EMDB-49208: Consensus map of the autoinhibitory unliganded CD163 trimer (map A) -
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Open data
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Basic information
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Title | Consensus map of the autoinhibitory unliganded CD163 trimer (map A) | |||||||||
![]() | CD163_Trimer_Consensus_Map_A_sharpen | |||||||||
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![]() | CD163 / M130 / Scavenger receptor / ENDOCYTOSIS | |||||||||
Function / homology | ![]() 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 | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Huang C-S / White JBR / Degtjarik O | |||||||||
Funding support | ![]()
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![]() | ![]() Title: 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. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 230.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.5 KB 21.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.1 KB | Display | ![]() |
Images | ![]() | 86 KB | ||
Masks | ![]() | 244.1 MB | ![]() | |
Filedesc metadata | ![]() | 5.7 KB | ||
Others | ![]() ![]() | 226.4 MB 226.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 853.8 KB | Display | ![]() |
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Full document | ![]() | 853.3 KB | Display | |
Data in XML | ![]() | 22 KB | Display | |
Data in CIF | ![]() | 28.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9nb5C ![]() 9nb6C ![]() 9nb8C C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | CD163_Trimer_Consensus_Map_A_sharpen | ||||||||||||||||||||||||||||||||||||
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
-Mask #1
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Projections & Slices |
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Density Histograms |
-Half map: CD163 Trimer Consensus half map 1
File | emd_49208_half_map_1.map | ||||||||||||
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Annotation | CD163_Trimer_Consensus_half_map_1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: CD163 Trimer Consensus half map 2
File | emd_49208_half_map_2.map | ||||||||||||
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Annotation | CD163_Trimer_Consensus_half_map_2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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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: all |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 400 KDa |
-Macromolecule #1: CD163
Macromolecule | Name: CD163 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: SSLGGTDKEL RLVDGENKCS GRVEVKVQEE WGTVCNNGWS MEAVSVICNQ LGCPTAIKAP GWANSSAGSG RIWMDHVSCR GNESALWDCK HDGWGKHSNC THQQDAGVTC SDGSNLEMRL TRGGNMCSGR IEIKFQGRWG TVCDDNFNID HASVICRQLE CGSAVSFSGS ...String: SSLGGTDKEL RLVDGENKCS GRVEVKVQEE WGTVCNNGWS MEAVSVICNQ LGCPTAIKAP GWANSSAGSG RIWMDHVSCR GNESALWDCK HDGWGKHSNC THQQDAGVTC SDGSNLEMRL TRGGNMCSGR IEIKFQGRWG TVCDDNFNID HASVICRQLE CGSAVSFSGS SNFGEGSGPI WFDDLICNGN ESALWNCKHQ GWGKHNCDHA EDAGVICSKG ADLSLRLVDG VTECSGRLEV RFQGEWGTIC DDGWDSYDAA VACKQLGCPT AVTAIGRVNA SKGFGHIWLD SVSCQGHEPA IWQCKHHEWG KHYCNHNEDA GVTCSDGSDL ELRLRGGGSR CAGTVEVEIQ RLLGKVCDRG WGLKEADVVC RQLGCGSALK TSYQVYSKIQ ATNTWLFLSS CNGNETSLWD CKNWQWGGLT CDHYEEAKIT CSAHREPRLV GGDIPCSGRV EVKHGDTWGS ICDSDFSLEA ASVLCRELQC GTVVSILGGA HFGEGNGQIW AEEFQCEGHE SHLSLCPVAP RPEGTCSHSR DVGVVCSRYT EIRLVNGKTP CEGRVELKTL GAWGSLCNSH WDIEDAHVLC QQLKCGVALS TPGGARFGKG NGQIWRHMFH CTGTEQHMGD CPVTALGASL CPSEQVASVI CSGNQSQTLS SCNSSSLGPT RPTIPEESAV ACIESGQLRL VNGGGRCAGR VEIYHEGSWG TICDDSWDLS DAHVVCRQLG CGEAINATGS AHFGEGTGPI WLDEMKCNGK ESRIWQCHSH GWGQQNCRHK EDAGVICSEF MSLRLTSEAS REACAGRLEV FYNGAWGTVG KSSMSETTVG VVCRQLGCAD KGKINPASLD KAMSIPMWVD NVQCPKGPDT LWQCPSSPWE KRLASPSEET WITCDNKIRL QEGPTSCSGR VEIWHGGSWG TVCDDSWDLD DAQVVCQQLG CGPALKAFKE AEFGQGTGPI WLNEVKCKGN ESSLWDCPAR RWGHSECGHK EDAAVNCTDI SVQKTPQKAT TGRSHHHHHH HH UniProtKB: Scavenger receptor cysteine-rich type 1 protein M130 |
-Macromolecule #2: CD163
Macromolecule | Name: CD163 / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: SSLGGTDKEL RLVDGENKCS GRVEVKVQEE WGTVCNNGWS MEAVSVICNQ LGCPTAIKAP GWANSSAGSG RIWMDHVSCR GNESALWDCK HDGWGKHSNC THQQDAGVTC SDGSNLEMRL TRGGNMCSGR IEIKFQGRWG TVCDDNFNID HASVICRQLE CGSAVSFSGS ...String: SSLGGTDKEL RLVDGENKCS GRVEVKVQEE WGTVCNNGWS MEAVSVICNQ LGCPTAIKAP GWANSSAGSG RIWMDHVSCR GNESALWDCK HDGWGKHSNC THQQDAGVTC SDGSNLEMRL TRGGNMCSGR IEIKFQGRWG TVCDDNFNID HASVICRQLE CGSAVSFSGS SNFGEGSGPI WFDDLICNGN ESALWNCKHQ GWGKHNCDHA EDAGVICSKG ADLSLRLVDG VTECSGRLEV RFQGEWGTIC DDGWDSYDAA VACKQLGCPT AVTAIGRVNA SKGFGHIWLD SVSCQGHEPA IWQCKHHEWG KHYCNHNEDA GVTCSDGSDL ELRLRGGGSR CAGTVEVEIQ RLLGKVCDRG WGLKEADVVC RQLGCGSALK TSYQVYSKIQ ATNTWLFLSS CNGNETSLWD CKNWQWGGLT CDHYEEAKIT CSAHREPRLV GGDIPCSGRV EVKHGDTWGS ICDSDFSLEA ASVLCRELQC GTVVSILGGA HFGEGNGQIW AEEFQCEGHE SHLSLCPVAP RPEGTCSHSR DVGVVCSRYT EIRLVNGKTP CEGRVELKTL GAWGSLCNSH WDIEDAHVLC QQLKCGVALS TPGGARFGKG NGQIWRHMFH CTGTEQHMGD CPVTALGASL CPSEQVASVI CSGNQSQTLS SCNSSSLGPT RPTIPEESAV ACIESGQLRL VNGGGRCAGR VEIYHEGSWG TICDDSWDLS DAHVVCRQLG CGEAINATGS AHFGEGTGPI WLDEMKCNGK ESRIWQCHSH GWGQQNCRHK EDAGVICSEF MSLRLTSEAS REACAGRLEV FYNGAWGTVG KSSMSETTVG VVCRQLGCAD KGKINPASLD KAMSIPMWVD NVQCPKGPDT LWQCPSSPWE KRLASPSEET WITCDNKIRL QEGPTSCSGR VEIWHGGSWG TVCDDSWDLD DAQVVCQQLG CGPALKAFKE AEFGQGTGPI WLNEVKCKGN ESSLWDCPAR RWGHSECGHK EDAAVNCTDI SVQKTPQKAT TGRSHHHHHH HH UniProtKB: Scavenger receptor cysteine-rich type 1 protein M130 |
-Macromolecule #3: CD163
Macromolecule | Name: CD163 / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: SSLGGTDKEL RLVDGENKCS GRVEVKVQEE WGTVCNNGWS MEAVSVICNQ LGCPTAIKAP GWANSSAGSG RIWMDHVSCR GNESALWDCK HDGWGKHSNC THQQDAGVTC SDGSNLEMRL TRGGNMCSGR IEIKFQGRWG TVCDDNFNID HASVICRQLE CGSAVSFSGS ...String: SSLGGTDKEL RLVDGENKCS GRVEVKVQEE WGTVCNNGWS MEAVSVICNQ LGCPTAIKAP GWANSSAGSG RIWMDHVSCR GNESALWDCK HDGWGKHSNC THQQDAGVTC SDGSNLEMRL TRGGNMCSGR IEIKFQGRWG TVCDDNFNID HASVICRQLE CGSAVSFSGS SNFGEGSGPI WFDDLICNGN ESALWNCKHQ GWGKHNCDHA EDAGVICSKG ADLSLRLVDG VTECSGRLEV RFQGEWGTIC DDGWDSYDAA VACKQLGCPT AVTAIGRVNA SKGFGHIWLD SVSCQGHEPA IWQCKHHEWG KHYCNHNEDA GVTCSDGSDL ELRLRGGGSR CAGTVEVEIQ RLLGKVCDRG WGLKEADVVC RQLGCGSALK TSYQVYSKIQ ATNTWLFLSS CNGNETSLWD CKNWQWGGLT CDHYEEAKIT CSAHREPRLV GGDIPCSGRV EVKHGDTWGS ICDSDFSLEA ASVLCRELQC GTVVSILGGA HFGEGNGQIW AEEFQCEGHE SHLSLCPVAP RPEGTCSHSR DVGVVCSRYT EIRLVNGKTP CEGRVELKTL GAWGSLCNSH WDIEDAHVLC QQLKCGVALS TPGGARFGKG NGQIWRHMFH CTGTEQHMGD CPVTALGASL CPSEQVASVI CSGNQSQTLS SCNSSSLGPT RPTIPEESAV ACIESGQLRL VNGGGRCAGR VEIYHEGSWG TICDDSWDLS DAHVVCRQLG CGEAINATGS AHFGEGTGPI WLDEMKCNGK ESRIWQCHSH GWGQQNCRHK EDAGVICSEF MSLRLTSEAS REACAGRLEV FYNGAWGTVG KSSMSETTVG VVCRQLGCAD KGKINPASLD KAMSIPMWVD NVQCPKGPDT LWQCPSSPWE KRLASPSEET WITCDNKIRL QEGPTSCSGR VEIWHGGSWG TVCDDSWDLD DAQVVCQQLG CGPALKAFKE AEFGQGTGPI WLNEVKCKGN ESSLWDCPAR RWGHSECGHK EDAAVNCTDI SVQKTPQKAT TGRSHHHHHH HH UniProtKB: Scavenger receptor cysteine-rich type 1 protein M130 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | 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 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE |
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: ![]() |
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 |