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TitleFab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.
Journal, issue, pagesCell, Vol. 184, Issue 11, Page 2955-2972.e25, Year 2021
Publish dateMay 27, 2021
AuthorsWilton B Williams / R Ryan Meyerhoff / R J Edwards / Hui Li / Kartik Manne / Nathan I Nicely / Rory Henderson / Ye Zhou / Katarzyna Janowska / Katayoun Mansouri / Sophie Gobeil / Tyler Evangelous / Bhavna Hora / Madison Berry / A Yousef Abuahmad / Jordan Sprenz / Margaret Deyton / Victoria Stalls / Megan Kopp / Allen L Hsu / Mario J Borgnia / Guillaume B E Stewart-Jones / Matthew S Lee / Naomi Bronkema / M Anthony Moody / Kevin Wiehe / Todd Bradley / S Munir Alam / Robert J Parks / Andrew Foulger / Thomas Oguin / Gregory D Sempowski / Mattia Bonsignori / Celia C LaBranche / David C Montefiori / Michael Seaman / Sampa Santra / John Perfect / Joseph R Francica / Geoffrey M Lynn / Baptiste Aussedat / William E Walkowicz / Richard Laga / Garnett Kelsoe / Kevin O Saunders / Daniela Fera / Peter D Kwong / Robert A Seder / Alberto Bartesaghi / George M Shaw / Priyamvada Acharya / Barton F Haynes /
PubMed AbstractNatural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) ...Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (V) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without V-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgMIgDCD27, thus suggesting that they originated from a pool of antigen-experienced IgM or marginal zone B cells.
External linksCell / PubMed:34019795 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.61 - 7.0 Å
Structure data

EMDB-23094, PDB-7l02:
Cryo-EM structure of SARS-CoV-2 2P S ectodomain bound to one copy of domain-swapped antibody 2G12
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-23095, PDB-7l06:
Cryo-EM structure of SARS-CoV-2 2P S ectodomain bound to two copies of domain-swapped antibody 2G12
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-23097, PDB-7l09:
Cryo-EM structure of SARS-CoV-2 2P S ectodomain bound domain-swapped antibody 2G12 from masked 3D refinement
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-23124: Cryo-electron microcospy reconstruction of CH848.3.D0949.10.17chim.6R.DS.SOSIP.664 HIV Env
PDB-7l6o: Cryo-EM structure of HIV-1 Env CH848.3.D0949.10.17chim.6R.DS.SOSIP.664
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-23145: Cryo-electron microscopy reconstruction of locally refined antibody DH898.1 Fab-dimer
PDB-7l6m: Cryo-EM structure of DH898.1 Fab-dimer from local refinement of the Fab-dimer bound near the CD4 binding site of HIV-1 Env CH848 SOSIP trimer
Method: EM (single particle) / Resolution: 4.8 Å

EMDB-23152:
Cryo-electron microscopy reconstruction of antibody DH898.1 Fab-dimer bound to glycans 332, 392, and 396 of HIV Env CH848 10.17 SOSIP trimer
Method: EM (single particle) / Resolution: 6.1 Å

EMDB-23153:
Cryo-electron microscopy local refinement of antibody DH898.1 Fab-dimer bound to glycans 332, 392, and 396 of HIV Env CH848 10.17 SOSIP trimer
Method: EM (single particle) / Resolution: 7.0 Å

EMDB-23518: Cryo-EM map of DH851.3 bound to HIV-1 CH505 Env
PDB-7lu9: Cryo-EM structure of DH851.3 bound to HIV-1 CH505 Env
Method: EM (single particle) / Resolution: 5.6 Å

EMDB-23519: Cryo-EM map of DH898.1 Fab-dimer bound near the CD4 binding site of HIV-1 Env CH848 SOSIP trimer
PDB-7lua: Cryo-EM structure of DH898.1 Fab-dimer bound near the CD4 binding site of HIV-1 Env CH848 SOSIP trimer
Method: EM (single particle) / Resolution: 4.7 Å

PDB-6vtu:
DH717.1 Fab monomer in complex with man9 glycan
Method: X-RAY DIFFRACTION / Resolution: 2.61 Å

PDB-6xrj:
Crystal structure of the disulfide linked DH717.1 Fab dimer, derived from a macaque HIV-1 vaccine-induced Env glycan-reactive neutralizing antibody B cell lineage
Method: X-RAY DIFFRACTION / Resolution: 3.15 Å

Chemicals

ChemComp-GOL:
GLYCEROL

ChemComp-HOH:
WATER

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

Source
  • Severe acute respiratory syndrome-related coronavirus
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
  • human immunodeficiency virus 1
  • macaca mulatta (Rhesus monkey)
  • simian-human immunodeficiency virus
KeywordsIMMUNE SYSTEM / FAB FRAGMENT / HIV-1 / ANTIBODY / Fab-dimerized / glycan-reactive / antibodies / HIV / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex / SARS / COVID19 / SARS-CoV-2 2P S ectodomain / VIRAL PROTEIN-IMMUNE SYSTEM complex SARS-CoV-2 2P S ectodomain / DH898.1 / Fab-dimer / glycan-reactive neutralizing antibody / macaque HIV-1 vaccine-induced / B cell lineage / VIRAL PROTEIN / HIV-1 Env

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