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  • Structural basis for divers...
    Pancera, Marie; Shahzad-Ul-Hussan, Syed; Doria-Rose, Nicole A; McLellan, Jason S; Bailer, Robert T; Dai, Kaifan; Loesgen, Sandra; Louder, Mark K; Staupe, Ryan P; Yang, Yongping; Zhang, Baoshan; Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E; Blinn, Julie; Alam, S Munir; Haynes, Barton F; Amin, Mohammed N; Wang, Lai-Xi; Burton, Dennis R; Koff, Wayne C; Nabel, Gary J; Mascola, John R; Bewley, Carole A; Kwong, Peter D

    Nature Structural & Molecular Biology, 07/2013, Letnik: 20, Številka: 7
    Journal Article

    HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1-V2, showing an epitope comprising both high mannose-type and complex-type N-linked glycans. We combined structure, NMR and mutagenesis analyses to characterize glycan recognition by PG9 and PG16. Three PG16-specific residues, arginine, serine and histidine (RSH), were critical for binding sialic acid on complex-type glycans, and introduction of these residues into PG9 produced a chimeric antibody with enhanced HIV-1 neutralization. Although HIV-1-glycan diversity facilitates evasion, antibody somatic diversity can overcome this and can provide clues to guide the design of modified antibodies with enhanced neutralization.