[English] 日本語
Yorodumi
- EMDB-49218: Composite map of the CD163/Hp(1-1)Hb complex (Map K) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-49218
TitleComposite map of the CD163/Hp(1-1)Hb complex (Map K)
Map data
Sample
  • Complex: CD163/Hp(1-1)Hb complex
    • Protein or peptide: Isoform 2 of Haptoglobin
  • Protein or peptide: Scavenger receptor cysteine-rich type 1 protein M130
  • Protein or peptide: Hemoglobin subunit alpha
  • Protein or peptide: Hemoglobin subunit beta
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: PROTOPORPHYRIN IX CONTAINING FE
  • Ligand: OXYGEN MOLECULE
KeywordsCD163 / M130 / Scavenger receptor / Haptoglobin / Hemoglobin / Hb / Hp / HpHb / Hp(1-1)Hb / hemolysis / 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: 3.3 Å
AuthorsHuang C-S / White JBR / Degtjarik O
Funding support United Kingdom, 2 items
OrganizationGrant numberCountry
Wellcome Trust108466/Z/15/Z United Kingdom
Wellcome Trust221524/Z/20/Z United Kingdom
CitationJournal: PLoS Biol / Year: 2025
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
DepositionFeb 13, 2025-
Header (metadata) releaseJun 18, 2025-
Map releaseJun 18, 2025-
UpdateJul 23, 2025-
Current statusJul 23, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_49218.png

Downloads & links

-
Map

FileDownload / File: emd_49218.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.11 Å/pix.
x 400 pix.
= 444. Å		1.11 Å/pix.
x 400 pix.
= 444. Å		1.11 Å/pix.
x 400 pix.
= 444. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.11 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.55
Minimum - Maximum0.0 - 6.5136485
Average (Standard dev.)0.013744714 (±0.06973671)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 444.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Sample components

-
Entire : CD163/Hp(1-1)Hb complex

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

-
Supramolecule #1: CD163/Hp(1-1)Hb complex

SupramoleculeName: CD163/Hp(1-1)Hb complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #4
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 530 KDa

-
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: 109.731555 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 ATTGRSHHHH HHHH

UniProtKB: Scavenger receptor cysteine-rich type 1 protein M130

-
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

-
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

-
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

-
Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 9 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

-
Macromolecule #6: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 6 / Number of copies: 23 / Formula: CA
Molecular weightTheoretical: 40.078 Da

-
Macromolecule #7: PROTOPORPHYRIN IX CONTAINING FE

MacromoleculeName: PROTOPORPHYRIN IX CONTAINING FE / type: ligand / ID: 7 / Number of copies: 2 / Formula: HEM
Molecular weightTheoretical: 616.487 Da
Chemical component information

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE

-
Macromolecule #8: OXYGEN MOLECULE

MacromoleculeName: OXYGEN MOLECULE / type: ligand / ID: 8 / Number of copies: 2 / Formula: OXY
Molecular weightTheoretical: 31.999 Da
Chemical component information

ChemComp-O2:
OXYGEN MOLECULE

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.1 mg/mL
BufferpH: 7.5
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: TFS Selectris / Energy filter - Slit width: 10 eV
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.6 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.9 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 2709108
CTF correctionSoftware - Name: cryoSPARC (ver. 4.4.1) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.4.1) / Number images used: 245961
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.4.1)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.4.1)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more