Structure and immune recognition of trimeric pre-fusion HIV-1 Env [electronic resource].
- Bethesda, Md. : National Institutes of Health (U.S.), 2014. and Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy
- Physical Description:
- pages 455-461 : digital, PDF file
- Additional Creators:
- Argonne National Laboratory, National Institutes of Health (U.S.), United States. Department of Energy. Office of Basic Energy Sciences, and United States. Department of Energy. Office of Scientific and Technical Information
- 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. In conclusion, 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.
- Published through SciTech Connect., 10/08/2014., Nature (London) 514 7523 ISSN 0028-0836 AM, and Marie Pancera; Tongqing Zhou; Aliaksandr Druz; Ivelin S. Georgiev; Cinque Soto; Jason Gorman; Jinghe Huang; Priyamvada Acharya; Gwo-Yu Chuang; Gilad Ofek; Guillaume B. E. Stewart-Jones; Jonathan Stuckey; Robert T. Bailer; M. Gordon Joyce; Mark K. Louder; Nancy Tumba; Yongping Yang; Baoshan Zhang; Myron S. Cohen; Barton F. Haynes; John R. Mascola; Lynn Morris; James B. Munro; Scott C. Blanchard; Walther Mothes; Mark Connors; Peter D. Kwong.
- Funding Information:
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