A sequestered fusion peptide in the structure of an HIV-1 transmitted founder envelope trimer
Open Access
- 20 February 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 10 (1), 1-10
- https://doi.org/10.1038/s41467-019-08825-7
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.Keywords
This publication has 69 references indexed in Scilit:
- RELION: Implementation of a Bayesian approach to cryo-EM structure determinationJournal of Structural Biology, 2012
- Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimerNature Structural & Molecular Biology, 2012
- Broad neutralization coverage of HIV by multiple highly potent antibodiesNature, 2011
- Toward the estimation of the absolute quality of individual protein structure modelsBioinformatics, 2010
- Features and development of CootActa crystallographica. Section D, Structural biology, 2010
- PHENIX: a comprehensive Python-based system for macromolecular structure solutionActa crystallographica. Section D, Structural biology, 2010
- MolProbity: all-atom structure validation for macromolecular crystallographyActa crystallographica. Section D, Structural biology, 2009
- Viral membrane fusionNature Structural & Molecular Biology, 2008
- Visualizing density maps with UCSF ChimeraJournal of Structural Biology, 2007
- Automated molecular microscopy: The new Leginon systemJournal of Structural Biology, 2005