4TVP

Crystal Structure of the HIV-1 BG505 SOSIP.664 Env Trimer Ectodomain, Comprising Atomic-Level Definition of Pre-Fusion gp120 and gp41, in Complex with Human Antibodies PGT122 and 35O22

Summary for 4TVP

• Entry DOI: 10.2210/pdb4tvp/pdb
• Descriptor: Envelope glycoprotein gp160, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (16 entities in total)
• Functional Keywords: hiv-1 envelope trimer, gp120, gp41, membrane fusion, viral entry, viral protein-immune system complex, type-1 membrane fusion glycoprotein, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 181416.23

Authors

Pancera, M.,Zhou, T.,Kwong, P.D. (deposition date: 2014-06-27, release date: 2014-10-08, Last modification date: 2024-10-30)

Primary citation

Pancera, M.,Zhou, T.,Druz, A.,Georgiev, I.S.,Soto, C.,Gorman, J.,Huang, J.,Acharya, P.,Chuang, G.Y.,Ofek, G.,Stewart-Jones, G.B.,Stuckey, J.,Bailer, R.T.,Joyce, M.G.,Louder, M.K.,Tumba, N.,Yang, Y.,Zhang, B.,Cohen, M.S.,Haynes, B.F.,Mascola, J.R.,Morris, L.,Munro, J.B.,Blanchard, S.C.,Mothes, W.,Connors, M.,Kwong, P.D.
Structure and immune recognition of trimeric pre-fusion HIV-1 Env.
Nature, 514:455-461, 2014

PubMed Abstract: 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.

PubMed: 25296255
DOI: 10.1038/nature13808

Experimental method

X-RAY DIFFRACTION (3.1 Å)