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

Citation:
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 A 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.
PDB ID: 4TVPDownload
MMDB ID: 123691
PDB Deposition Date: 2014/6/27
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 3.1  Å
Source Organism:
Human immunodeficiency virus 1
Similar Structures:
Biological Unit for 4TVP: octadecameric; determined by author
Molecular Components in 4TVP
Label Count Molecule
Proteins (18 molecules)
3
Envelope Glycoprotein Gp160
Molecule annotation
3
Envelope Glycoprotein Gp160
Molecule annotation
3
Pgt122 Light Chain
Molecule annotation
3
Pgt122 Heavy Chain
Molecule annotation
3
35o22 Heavy Chain
Molecule annotation
3
35o22 Light Chain
Molecule annotation
Chemicals (148 molecules)
1
84
2
9
3
30
4
25
* Click molecule labels to explore molecular sequence information.

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