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

Summary for 6XRJ

• Entry DOI: 10.2210/pdb6xrj/pdb
• Related: 7L02 7L06 7L09
• Descriptor: DH717.1 heavy chain Fab fragment, DH717.1 light chain Fab fragment (2 entities in total)
• Functional Keywords: fab-dimerized, glycan-reactive, antibodies, hiv, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 185301.85

Authors

Manne, K.,Nicely, N.I.,Acharya, P. (deposition date: 2020-07-13, release date: 2020-12-30, Last modification date: 2024-10-23)

Primary citation

Williams, W.B.,Meyerhoff, R.R.,Edwards, R.J.,Li, H.,Manne, K.,Nicely, N.I.,Henderson, R.,Zhou, Y.,Janowska, K.,Mansouri, K.,Gobeil, S.,Evangelous, T.,Hora, B.,Berry, M.,Abuahmad, A.Y.,Sprenz, J.,Deyton, M.,Stalls, V.,Kopp, M.,Hsu, A.L.,Borgnia, M.J.,Stewart-Jones, G.B.E.,Lee, M.S.,Bronkema, N.,Moody, M.A.,Wiehe, K.,Bradley, T.,Alam, S.M.,Parks, R.J.,Foulger, A.,Oguin, T.,Sempowski, G.D.,Bonsignori, M.,LaBranche, C.C.,Montefiori, D.C.,Seaman, M.,Santra, S.,Perfect, J.,Francica, J.R.,Lynn, G.M.,Aussedat, B.,Walkowicz, W.E.,Laga, R.,Kelsoe, G.,Saunders, K.O.,Fera, D.,Kwong, P.D.,Seder, R.A.,Bartesaghi, A.,Shaw, G.M.,Acharya, P.,Haynes, B.F.
Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.
Cell, 184:2955-, 2021

PubMed Abstract: 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.

PubMed: 34019795
DOI: 10.1016/j.cell.2021.04.042

Experimental method

X-RAY DIFFRACTION (3.15 Å)