Pancera, Marie.Zhou, Tongqing.Druz, Aliaksandr.Georgiev, Ivelin S.Soto, Cinque.Gorman, Jason.Huang, Jinghe.Acharya, Priyamvada.Chuang, Gwo-Yu.Ofek, Gilad.Stewart-Jones, Guillaume B. E.Stuckey, Jonathan.Bailer, Robert T.Joyce, M. Gordon.Louder, Mark K.Tumba, Nancy Lola.Yang, Yongping.Zhang, Baoshan.Cohen, Myron S.Haynes, Barton F.Mascola, John R.Morris, Lynn.Munro, James B.Blanchard, Scott C.Mothes, Walther.Connors, Mark.Kwong, Peter D.2016-11-082016-11-0820142014Pancera, M., Zhou, T., Druz, A., Georgiev, I.S., Soto, C., Gorman, J., Huang, J., Acharya, P., Chuang, G.Y., Ofek, G. and Stewart-Jones, G.B.E., Stuckey, J., Bailer, R.T., Joyce, M.G., Louder, M.K., Tumba, N., Yang, Y., Zhang, B., Cohen, M.S., Barton F. Haynes, B.F., Mascola, J.R., Morris, L., Munro, J.B., Blanchard, S.C., Mothes, W., Connors, M.and Kwong, P.D. 2014. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514(7523), 455-461.http://dx.doi.org/10.1038/nature13808http://hdl.handle.net/10413/13619CAPRISA, 2014.The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 Å resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation.enAIDS Vaccines/chemistry.AIDS Vaccines/immunology.Amino Acid Sequence.Cohort Studies.Crystallography, X-Ray.Genetic Variation.Glycosylation.Peer reviewed journal article