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- EMDB-63244: Cryo-EM structure of human FcRL5 bound to IgG-Fc -

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Basic information

Entry
Database: EMDB / ID: EMD-63244
TitleCryo-EM structure of human FcRL5 bound to IgG-Fc
Map dataCryo-EM global map sharp of FcRL5 in complex with human IgG.
Sample
  • Complex: Complex of human FcRL5 with IgG-Fc
    • Protein or peptide: Fc receptor-like protein 5
    • Protein or peptide: Immunoglobulin gamma-1 heavy chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsIgG / FcRL5 / IMMUNE SYSTEM
Function / homology
Function and homology information


B cell activation / immunoglobulin complex / single fertilization / coreceptor activity / transmembrane signaling receptor activity / adaptive immune response / cell surface receptor signaling pathway / receptor complex / immune response / external side of plasma membrane ...B cell activation / immunoglobulin complex / single fertilization / coreceptor activity / transmembrane signaling receptor activity / adaptive immune response / cell surface receptor signaling pathway / receptor complex / immune response / external side of plasma membrane / cell surface / extracellular region / plasma membrane
Similarity search - Function
: / Immunoglobulin domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. ...: / Immunoglobulin domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin subtype / Immunoglobulin / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Immunoglobulin gamma-1 heavy chain / Fc receptor-like protein 5
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.56 Å
AuthorsChen SH / Xiao JY
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Sci Adv / Year: 2026
Title: Human FcRL5 is an Fc receptor that simultaneously engages two IgGs.
Authors: Shihua Chen / Shuhan Li / Zhiying Zhang / Junyu Xiao /
Abstract: The Fc receptors play crucial roles in initiating the effector functions of immunoglobulins. FcRL5 is a prominent target in B cell malignancies and has been implicated as a receptor for ...The Fc receptors play crucial roles in initiating the effector functions of immunoglobulins. FcRL5 is a prominent target in B cell malignancies and has been implicated as a receptor for immunoglobulin G (IgG). However, the molecular mechanism remained unclear. Here, we demonstrate that human FcRL5, but not its mouse counterpart, is a bona fide IgG-Fc (Fcγ) receptor that uniquely requires the presence of two Fcγ molecules in close proximity to form a robust interaction. Cryo-electron microscopy reveals that FcRL5 optimally engages two Fcγ molecules positioned at a 60° angle, with its D1-D2 domains binding to the first Fcγ molecule, while its D3 domain arches over the second Fcγ. This distinctive binding capability enables FcRL5 to specifically recognize IgG immune complexes (ICs), with the binding strength correlating with IgG concentration in the ICs. In addition, we demonstrate that FcRL5 can internalize the IgG polymer and IC. These results shed light on FcRL5 function and reveal a unique Fcγ-FcγR binding mode governed by avidity.
History
DepositionJan 23, 2025-
Header (metadata) releaseNov 26, 2025-
Map releaseNov 26, 2025-
UpdateJan 21, 2026-
Current statusJan 21, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_63244.map.gz / Format: CCP4 / Size: 209.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryo-EM global map sharp of FcRL5 in complex with human IgG.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 380 pix.
= 406.6 Å
1.07 Å/pix.
x 380 pix.
= 406.6 Å
1.07 Å/pix.
x 380 pix.
= 406.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.07 Å
Density
Contour LevelBy AUTHOR: 0.167
Minimum - Maximum-0.54746056 - 1.0027467
Average (Standard dev.)-0.0003163872 (±0.022227257)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions380380380
Spacing380380380
CellA=B=C: 406.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: Cryo-EM global map half A of FcRL5 in complex with human IgG.

Fileemd_63244_half_map_1.map
AnnotationCryo-EM global map half A of FcRL5 in complex with human IgG.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: Cryo-EM global map half B of FcRL5 in complex with human IgG.

Fileemd_63244_half_map_2.map
AnnotationCryo-EM global map half B of FcRL5 in complex with human IgG.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Complex of human FcRL5 with IgG-Fc

EntireName: Complex of human FcRL5 with IgG-Fc
Components
  • Complex: Complex of human FcRL5 with IgG-Fc
    • Protein or peptide: Fc receptor-like protein 5
    • Protein or peptide: Immunoglobulin gamma-1 heavy chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Complex of human FcRL5 with IgG-Fc

SupramoleculeName: Complex of human FcRL5 with IgG-Fc / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Fc receptor-like protein 5

MacromoleculeName: Fc receptor-like protein 5 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 94.512047 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QFARTPRPII FLQPPWTTVF QGERVTLTCK GFRFYSPQKT KWYHRYLGKE ILRETPDNIL EVQESGEYRC QAQGSPLSSP VHLDFSSAS LILQAPLSVF EGDSVVLRCR AKAEVTLNNT IYKNDNVLAF LNKRTDFHIP HACLKDNGAY RCTGYKESCC P VSSNTVKI ...String:
QFARTPRPII FLQPPWTTVF QGERVTLTCK GFRFYSPQKT KWYHRYLGKE ILRETPDNIL EVQESGEYRC QAQGSPLSSP VHLDFSSAS LILQAPLSVF EGDSVVLRCR AKAEVTLNNT IYKNDNVLAF LNKRTDFHIP HACLKDNGAY RCTGYKESCC P VSSNTVKI QVQEPFTRPV LRASSFQPIS GNPVTLTCET QLSLERSDVP LRFRFFRDDQ TLGLGWSLSP NFQITAMWSK DS GFYWCKA ATMPYSVISD SPRSWIQVQI PASHPVLTLS PEKALNFEGT KVTLHCETQE DSLRTLYRFY HEGVPLRHKS VRC ERGASI SFSLTTENSG NYYCTADNGL GAKPSKAVSL SVTVPVSHPV LNLSSPEDLI FEGAKVTLHC EAQRGSLPIL YQFH HEGAA LERRSANSAG GVAISFSLTA EHSGNYYCTA DNGFGPQRSK AVSLSVTVPV SHPVLTLSSA EALTFEGATV TLHCE VQRG SPQILYQFYH EDMPLWSSST PSVGRVSFSF SLTEGHSGNY YCTADNGFGP QRSEVVSLFV TVPVSRPILT LRVPRA QAV VGDLLELHCE APRGSPPILY WFYHEDVTLG SSSAPSGGEA SFNLSLTAEH SGNYSCEANN GLVAQHSDTI SLSVIVP VS RPILTFRAPR AQAVVGDLLE LHCEALRGSS PILYWFYHED VTLGKISAPS GGGASFNLSL TTEHSGIYSC EADNGLEA Q RSEMVTLKVA VPVSRPVLTL RAPGTHAAVG DLLELHCEAL RGSPLILYRF FHEDVTLGNR SSPSGGASLN LSLTAEHSG NYSCEADNGL GAQRSETVTL YITGLTANRS GPFATGHHHH HHHHWRPLES RVDYKDDDDK

UniProtKB: Fc receptor-like protein 5

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Macromolecule #2: Immunoglobulin gamma-1 heavy chain

MacromoleculeName: Immunoglobulin gamma-1 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 12 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 28.081764 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EPKSCDKTHT CPPCPAPELL GGPSVFLFPP KPKDTLMISR TPEVTCVVVD VSHEDPEVKF NWYVDGVEVH NAKTKPREEQ YNSTYRVVS VLTVCHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS RDELTKNQVS LTCLVKGFYP S DIAVEWES ...String:
EPKSCDKTHT CPPCPAPELL GGPSVFLFPP KPKDTLMISR TPEVTCVVVD VSHEDPEVKF NWYVDGVEVH NAKTKPREEQ YNSTYRVVS VLTVCHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS RDELTKNQVS LTCLVKGFYP S DIAVEWES NGQPENNYKT TPPVLDSDGS FFLYSKLTVD KSRWQQGNVF SCSVMHEALH NHYTQKSLDK STGKPTLYNV SL IMSDTGG TCY

UniProtKB: Immunoglobulin gamma-1 heavy chain

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Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 13 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

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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 TALOS ARCTICA
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: OTHER / Imaging mode: OTHER / Nominal defocus max: 1.7 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER / Details: AlphaFold predicted
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.56 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 257893
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

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