Fera, DanielaLee, MatthewWiehe, KevinMeyerhoff, R. RyanPiai, AlessandroBonsignori, MattiaAussedat, BaptisteWalkowicz, William E.Ton, ThereseZhou, Jeffrey O.Danishefsky, SamuelHaynes, Barton F.Harrison, Stephen2018-04-192018Fera, D., M. S. Lee, K. Wiehe, R. R. Meyerhoff, A. Piai, M. Bonsignori, B. Aussedat, et al. 2018. “HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope.” Nature Communications 9 (1): 1111. doi:10.1038/s41467-018-03565-6. http://dx.doi.org/10.1038/s41467-018-03565-6.http://nrs.harvard.edu/urn-3:HUL.InstRepos:35982207HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide (“Man9-V3”) for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage (“DH270”), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man9-V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs—the conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen.en-USJournal Article2018-04-1910.1038/s41467-018-03565-6