Structure of Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition
43 Pages Posted: 5 Aug 2019 Sneak Peek Status: Under ReviewMore...
Antibodies targeting the V1V2-apex of the HIV-1 envelope (Env) trimer comprise one of the most commonly elicited categories of broadly neutralizing antibodies. Structures of these antibodies indicate diverse modes of Env recognition typified by antibodies of the PG9 class and the PGT145 class. The mode of recognition, however, has been unclear for the most potent of the V1V2-apex-targeting antibodies, CAP256-VRC26.25 (named for donor-lineage.clone). Here we determine the cryo-electron microscopy structure at 3.8-Å resolution of the antigen-binding fragment of CAP256-VRC26.25 in complex with the Env trimer thought to have initiated the lineage. Remarkably, the 36-residue protruding loop of CAP256-VRC26.25 displayed recognition incorporating both strand-C interactions similar to the PG9 class and V1V2-apex insertion similar to the PGT145 class. Structural elements of separate antibody classes can thus intermingle to form a “combined” class, which in this case yields an antibody of extraordinary potency.
Keywords: broadly neutralizing antibody, HIV-1 envelope trimer, multidonor antibody class, PCT64, PG9, PGDM1400, PGT145, tyrosine sulfation, V1V2-apex recognition
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