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Structure and immune recognition of trimeric pre-fusion HIV-1 Env.

Publication ,  Journal Article
Pancera, M; Zhou, T; Druz, A; Georgiev, IS; Soto, C; Gorman, J; Huang, J; Acharya, P; Chuang, G-Y; Ofek, G; Stewart-Jones, GBE; Stuckey, J ...
Published in: Nature
October 23, 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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

October 23, 2014

Volume

514

Issue

7523

Start / End Page

455 / 461

Location

England

Related Subject Headings

  • Virus Internalization
  • Structural Homology, Protein
  • Protein Subunits
  • Protein Structure, Quaternary
  • Protein Multimerization
  • Polysaccharides
  • Molecular Sequence Data
  • Models, Molecular
  • Membrane Fusion
  • Immune Evasion
 

Citation

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Pancera, M., Zhou, T., Druz, A., Georgiev, I. S., Soto, C., Gorman, J., … Kwong, P. D. (2014). Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature, 514(7523), 455–461. https://doi.org/10.1038/nature13808
Pancera, Marie, Tongqing Zhou, Aliaksandr Druz, Ivelin S. Georgiev, Cinque Soto, Jason Gorman, Jinghe Huang, et al. “Structure and immune recognition of trimeric pre-fusion HIV-1 Env.Nature 514, no. 7523 (October 23, 2014): 455–61. https://doi.org/10.1038/nature13808.
Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, Gorman J, et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature. 2014 Oct 23;514(7523):455–61.
Pancera, Marie, et al. “Structure and immune recognition of trimeric pre-fusion HIV-1 Env.Nature, vol. 514, no. 7523, Oct. 2014, pp. 455–61. Pubmed, doi:10.1038/nature13808.
Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, Gorman J, Huang J, Acharya P, Chuang G-Y, Ofek G, Stewart-Jones GBE, Stuckey J, Bailer RT, Joyce MG, Louder MK, Tumba N, Yang Y, Zhang B, Cohen MS, Haynes BF, Mascola JR, Morris L, Munro JB, Blanchard SC, Mothes W, Connors M, Kwong PD. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature. 2014 Oct 23;514(7523):455–461.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

October 23, 2014

Volume

514

Issue

7523

Start / End Page

455 / 461

Location

England

Related Subject Headings

  • Virus Internalization
  • Structural Homology, Protein
  • Protein Subunits
  • Protein Structure, Quaternary
  • Protein Multimerization
  • Polysaccharides
  • Molecular Sequence Data
  • Models, Molecular
  • Membrane Fusion
  • Immune Evasion