Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions
Author(s) -
James B. Munro,
Jason Gorman,
Xiaochu Ma,
Zhou Zhou,
James Arthos,
Dennis R. Burton,
Wayne C. Koff,
Joel R. Courter,
Amos B. Smith,
Peter D. Kwong,
Scott C. Blanchard,
Walther Mothes
Publication year - 2014
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.1254426
Subject(s) - förster resonance energy transfer , neutralization , viral envelope , context (archaeology) , glycoprotein , biophysics , chemistry , immune escape , protein subunit , ligand (biochemistry) , human immunodeficiency virus (hiv) , protein structure , virology , virus , biology , fluorescence , receptor , immune system , biochemistry , gene , physics , genetics , quantum mechanics , paleontology
The HIV-1 envelope (Env) mediates viral entry into host cells. To enable the direct imaging of conformational dynamics within Env, we introduced fluorophores into variable regions of the glycoprotein gp120 subunit and measured single-molecule fluorescence resonance energy transfer within the context of native trimers on the surface of HIV-1 virions. Our observations revealed unliganded HIV-1 Env to be intrinsically dynamic, transitioning between three distinct prefusion conformations, whose relative occupancies were remodeled by receptor CD4 and antibody binding. The distinct properties of neutralization-sensitive and neutralization-resistant HIV-1 isolates support a dynamics-based mechanism of immune evasion and ligand recognition.
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