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Yorodumi- EMDB-70607: Composite map of six VRC35 Fabs and three MEDI8852 Fabs bound to ... -
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Basic information
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| Title | Composite map of six VRC35 Fabs and three MEDI8852 Fabs bound to influenza H3N2 Victoria 2011 hemagglutinin | |||||||||
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Keywords | broadly neutralizing antibody / cryo-EM / hemagglutinin / high mannose / homotypic interactions / influenza A virus / multimeric recognition / N-linked glycan / ANTIVIRAL PROTEIN / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
| Function / homology | Function and homology informationviral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / membrane Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() Influenza A virus | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Cheng J / Cale EM / Longo N / Sutton MS / Lei H / Huang R / Morton AJ / Lang ZC / Morano NC / Roark RS ...Cheng J / Cale EM / Longo N / Sutton MS / Lei H / Huang R / Morton AJ / Lang ZC / Morano NC / Roark RS / Becker JE / Tsybovsky Y / Li N / Zhang B / Du H / Rubin S / Shapiro L / Pierson TC / Doria-Rose NA / Kwong PD / Zhou T | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Adv Sci (Weinh) / Year: 2026Title: Canonical Antibodies Adopt Distinct Binding Modes to Recognize Viral Glycan Shields. Authors: Jiaxuan Cheng / Evan M Cale / Amirabbas Maghsoudi / Matthew S Sutton / Nancy S Longo / Rebecca A Gillespie / Lingshu Wang / Ivan Kosik / Sue Chong / Atsuhiro Yasuhara / Tatsiana Bylund / ...Authors: Jiaxuan Cheng / Evan M Cale / Amirabbas Maghsoudi / Matthew S Sutton / Nancy S Longo / Rebecca A Gillespie / Lingshu Wang / Ivan Kosik / Sue Chong / Atsuhiro Yasuhara / Tatsiana Bylund / Arne Schön / Prabhanshu Tripathi / Yaroslav Tsybovsky / Haotian Lei / Nicholas C Morano / Allison B Lupatkin / Abraham J Morton / Zabrina C Lang / Jordan E Becker / Isabella R Frascilla / Myungjin Lee / Ning Li / Cuiping Liu / Ryan S Roark / Chen-Hsiang Shen / I-Ting Teng / David J Van Wazer / Danyi Wang / Lingyuan Wu / Goran Ahlsen / Mike Castro / Haijuan Du / Michael J Ernandes / Tiansheng Li / Bob C Lin / Mark K Louder / Krisha McKee / Jonah S Merriam / Sijy O'Dell / Li Ou / Sergei Pletnev / David Prikryl / Qi Qiu / Sarah Rubin / Mallika Sastry / Stephen D Schmidt / Asif Shajahan / Andrea R Shiakolas / Sanjay Srivatsan / Baoshan Zhang / Qiong Zhou / Mark Connors / Jason G Gall / Yicheng Guo / Rick K Huang / Yaoxing Huang / Richard A Koup / Q Paula Lei / John R Mascola / Reda Rawi / Leonid Serebryannyy / Lawrence Shapiro / Zizhang Sheng / David D Ho / Patrick C Wilson / Jonathan W Yewdell / Theodore C Pierson / Masaru Kanekiyo / Nicole A Doria-Rose / Peter D Kwong / Tongqing Zhou / ![]() Abstract: Viral entry glycoproteins are often shielded from immune recognition by dense N-linked glycans that limit antibody access to protein epitopes. While glycan-reactive antibodies with unusual ...Viral entry glycoproteins are often shielded from immune recognition by dense N-linked glycans that limit antibody access to protein epitopes. While glycan-reactive antibodies with unusual architectures have been described, how canonical Y-shaped antibodies engage these glycan-rich surfaces remains poorly defined. Here, we characterize two human antibodies, VRC35 and VRC36, isolated from an HIV-1-infected donor, that recognize diverse glycosylated viral glycoproteins. Cryo-electron microscopy structural analyses of these antibodies in complex with viral entry glycoproteins, including HIV-1 envelope, influenza hemagglutinin, SARS-CoV-2 spike, and the Lassa virus glycoprotein complex, reveal adaptive Fab stoichiometries ranging from single-Fab binding to dimeric and higher-order assemblies are mediated by intra- and inter-IgG interactions that depend on local glycan organization. Dense glycan clustering on HIV-1 and influenza glycoproteins supports multivalent Fab assemblies and correlates with neutralization activity, whereas sparse glycan environments on SARS-CoV-2 and Lassa virus favor weak or heterogeneous engagement without neutralization. Structural and mutational analyses further demonstrate that homotypic Fab-Fab interactions stabilize multivalent engagement and contribute to neutralizing activity. Together, these findings define a structural framework in which viral glycan organization constrains antibody valency and engagement, while somatic hypermutation contributes to the acquisition of homotypic Fab-Fab interactions that facilitate multivalent recognition of viral glycan shields. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_70607.map.gz | 142.6 MB | EMDB map data format | |
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| Header (meta data) | emd-70607-v30.xml emd-70607.xml | 27.1 KB 27.1 KB | Display Display | EMDB header |
| Images | emd_70607.png | 108.4 KB | ||
| Filedesc metadata | emd-70607.cif.gz | 8.3 KB | ||
| Archive directory | https://data.pdbj.org/pub/emdb/structures/EMD-70607 ftp://data.pdbj.org/pub/emdb/structures/EMD-70607 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9om5MC ![]() 9npmC 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_70607.map.gz / Format: CCP4 / Size: 282.6 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: 0.83 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 : Complex of six VRC35 Fabs and three MEDI8852 Fabs bound to influe...
| Entire | Name: Complex of six VRC35 Fabs and three MEDI8852 Fabs bound to influenza H3N2 Victoria 2011 hemagglutinin |
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| Components |
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-Supramolecule #1: Complex of six VRC35 Fabs and three MEDI8852 Fabs bound to influe...
| Supramolecule | Name: Complex of six VRC35 Fabs and three MEDI8852 Fabs bound to influenza H3N2 Victoria 2011 hemagglutinin type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Hemagglutinin
| Macromolecule | Name: Hemagglutinin / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() Influenza A virus |
| Molecular weight | Theoretical: 38.937195 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MKTIIALSHI LCLVFAQKLP GNDNSTATLC LGHHAVPNGT IVKTICNDQI EVTNATELVQ NSSIGEICDS PHQILDGENC TLIDALLGD PQCDGFQNKK WDLFVERSKA YSNCYPYDVP DYASLRSLVA SSGTLEFNNE SFNWTGVTQN GTSSACIRRS N NSFFSRLN ...String: MKTIIALSHI LCLVFAQKLP GNDNSTATLC LGHHAVPNGT IVKTICNDQI EVTNATELVQ NSSIGEICDS PHQILDGENC TLIDALLGD PQCDGFQNKK WDLFVERSKA YSNCYPYDVP DYASLRSLVA SSGTLEFNNE SFNWTGVTQN GTSSACIRRS N NSFFSRLN WLTHLNFKYP ALNVTMPNNE QFDKLYIWGV HHPGTDKDQI FLYAQSSGRI TVSTKRSQQA VIPNIGSRPR IR NIPSRIS IYWTIVKPGD ILLINSTGNL IAPRGYFKIR SGKSSIMRSD APIGKCNSEC ITPNGSIPND KPFQNVNRIT YGA CPRYVK QSTLKLATGM RNVPEKQRRR RR UniProtKB: Hemagglutinin |
-Macromolecule #2: Hemagglutinin
| Macromolecule | Name: Hemagglutinin / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() Influenza A virus |
| Molecular weight | Theoretical: 25.410279 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: RGIFGAIAGF IENGWEGMVD GWYGFRHQNS EGRGQAADLK STQAAIDCIN GKLNRLIGKT NEKFHQIEKE FSEVEGRIQD LEKYVEDTK IDLWSYNAEL LVALENQHTI DLTDSEMNKL FEKTKKQLRE NAEDMGNGCF KIYHKCDNAC IGSIRNGTYD H DVYRDEAL ...String: RGIFGAIAGF IENGWEGMVD GWYGFRHQNS EGRGQAADLK STQAAIDCIN GKLNRLIGKT NEKFHQIEKE FSEVEGRIQD LEKYVEDTK IDLWSYNAEL LVALENQHTI DLTDSEMNKL FEKTKKQLRE NAEDMGNGCF KIYHKCDNAC IGSIRNGTYD H DVYRDEAL NNRFQIKGVS GLEVLFQGPG SGYIPEAPRD GQAYVRKDGE WVLLSTFLGH HHHHH UniProtKB: Hemagglutinin |
-Macromolecule #3: MEDI8852 Fab heavy chain
| Macromolecule | Name: MEDI8852 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 24.413189 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: QVQLQQSGPG LVKPSQTLSL TCAISGDSVS SYNAVWNWIR QSPSRGLEWL GRTYYRSGWY NDYAESVKSR ITINPDTSKN QFSLQLNSV TPEDTAVYYC ARSGHITVFG VNVDAFDMWG QGTMVTVSSA STKGPSVFPL APSSKSTSGT AALGCLVKDY F PEPVTVSW ...String: QVQLQQSGPG LVKPSQTLSL TCAISGDSVS SYNAVWNWIR QSPSRGLEWL GRTYYRSGWY NDYAESVKSR ITINPDTSKN QFSLQLNSV TPEDTAVYYC ARSGHITVFG VNVDAFDMWG QGTMVTVSSA STKGPSVFPL APSSKSTSGT AALGCLVKDY F PEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TKVDKKVEP |
-Macromolecule #4: MEDI8852 Fab light chain
| Macromolecule | Name: MEDI8852 Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 22.450832 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MTQSPSSLSA SVGDRVTITC RTSQSLSSYT HWYQQKPGKA PKLLIYAASS RGSGVPSRFS GSGSGTDFTL TISSLQPEDF ATYYCQQSR TFGQGTKVEI KRTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV QWKVDNALQS GNSQESVTEQ D SKDSTYSL ...String: MTQSPSSLSA SVGDRVTITC RTSQSLSSYT HWYQQKPGKA PKLLIYAASS RGSGVPSRFS GSGSGTDFTL TISSLQPEDF ATYYCQQSR TFGQGTKVEI KRTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV QWKVDNALQS GNSQESVTEQ D SKDSTYSL SSTLTLSKAD YEKHKVYACE VTHQGLSSPV TKSFNRGE |
-Macromolecule #5: VRC35 Fab heavy chain
| Macromolecule | Name: VRC35 Fab heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 6 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 23.90907 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: QVQLRQWGAG LVKPGETLSV TCELYGDSLR DFYWTWVRQA PGKPLQWVGE INVALNYKYN PSVRMTISVD EPKNQFTLKI FYTTAADTA TYFCARGRGT VATELAMWGP GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN S GALTSGVH ...String: QVQLRQWGAG LVKPGETLSV TCELYGDSLR DFYWTWVRQA PGKPLQWVGE INVALNYKYN PSVRMTISVD EPKNQFTLKI FYTTAADTA TYFCARGRGT VATELAMWGP GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN S GALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TKVDKKVEPK SCDK |
-Macromolecule #6: VRC35 Fab light chain
| Macromolecule | Name: VRC35 Fab light chain / type: protein_or_peptide / ID: 6 / Number of copies: 6 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 24.033865 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: NIVLTQTALS APVVLGQPAS ISCRSSETLH HSDGRTYLSW LHQGRGQPPR LLLYHISQRS FGVSDRISGR GAGTNFTLDI SKVEPEDAG LYYCMQATQF PRTFGPGTVL EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV ...String: NIVLTQTALS APVVLGQPAS ISCRSSETLH HSDGRTYLSW LHQGRGQPPR LLLYHISQRS FGVSDRISGR GAGTNFTLDI SKVEPEDAG LYYCMQATQF PRTFGPGTVL EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV TEQDSKDSTY SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE C |
-Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
| Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 10 / Number of copies: 3 / Formula: NAG |
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| Molecular weight | Theoretical: 221.208 Da |
| Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #11: alpha-D-mannopyranose
| Macromolecule | Name: alpha-D-mannopyranose / type: ligand / ID: 11 / Number of copies: 2 / Formula: MAN |
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| Molecular weight | Theoretical: 180.156 Da |
| Chemical component information | ![]() ChemComp-MAN: |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 54.5 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DARK 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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About Yorodumi



Keywords
Homo sapiens (human)
Influenza A virus
Authors
United States, 1 items
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Processing
FIELD EMISSION GUN

