A sequestered fusion peptide in the structure of an HIV-1 transmitted founder envelope trimer

Nature Communications
Neeti AnanthaswamyVenigalla B Rao

Abstract

The envelope protein of human immunodeficiency virus-1 (HIV-1) and its fusion peptide are essential for cell entry and vaccine design. Here, we describe the 3.9-Å resolution structure of an envelope protein trimer from a very early transmitted founder virus (CRF01_AE T/F100) complexed with Fab from the broadly neutralizing antibody (bNAb) 8ANC195. The overall T/F100 trimer structure is similar to other reported "closed" state prefusion trimer structures. In contrast, the fusion peptide, which is exposed to solvent in reported closed structures, is sequestered (buried) in the hydrophobic core of the T/F100 trimer. A buried conformation has previously been observed in "open" state structures formed after CD4 receptor binding. The T/F100 trimer binds poorly to bNAbs including the fusion peptide-specific bNAbs PGT151 and VRC34.01. The T/F100 structure might represent a prefusion state, intermediate between the closed and open states. These observations are relevant to mechanisms of HIV-1 transmission and vaccine design.

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Citations

Nov 26, 2019·Physical Chemistry Chemical Physics : PCCP·Lin-Tai Da, Mengna Lin
Dec 4, 2019·Expert Review of Vaccines·Iván Del Moral-Sánchez, Kwinten Sliepen
Aug 21, 2020·Journal of Virology·Raksha DasRaghavan Varadarajan
Oct 30, 2020·Viruses·Christophe CaillatWinfried Weissenhorn

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Datasets Mentioned

BETA
ID
ASM58958.1
AML29865.1
ASM59319.1

Methods Mentioned

BETA
X-ray
affinity purification
electrophoresis
glycosylation
ELISA
FRET
PCR
transfections
size
gel filtration

Software Mentioned

pdb
MotionCorr
Chimera
JSPR
MolProbity
RELION
Coot
Graphpad Prism
CARP
Phenix

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