HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations.
Xiaochu MaMaolin LuJason GormanDaniel S TerryXinyu HongZhou ZhouHong ZhaoRoger B AltmanJames ArthosScott C BlanchardPeter D KwongJames B MunroWalther MothesPublished in: eLife (2018)
HIV-1 entry into cells requires binding of the viral envelope glycoprotein (Env) to receptor CD4 and coreceptor. Imaging of individual Env molecules on native virions shows Env trimers to be dynamic, spontaneously transitioning between three distinct well-populated conformational states: a pre-triggered Env (State 1), a default intermediate (State 2) and a three-CD4-bound conformation (State 3), which can be stabilized by binding of CD4 and coreceptor-surrogate antibody 17b. Here, using single-molecule Fluorescence Resonance Energy Transfer (smFRET), we show the default intermediate configuration to be asymmetric, with individual protomers adopting distinct conformations. During entry, this asymmetric intermediate forms when a single CD4 molecule engages the trimer. The trimer can then transition to State 3 by binding additional CD4 molecules and coreceptor.
Keyphrases
- single molecule
- energy transfer
- antiretroviral therapy
- hiv infected
- hiv positive
- nk cells
- human immunodeficiency virus
- hepatitis c virus
- induced apoptosis
- high resolution
- hiv testing
- molecular dynamics simulations
- hiv aids
- oxidative stress
- men who have sex with men
- cell cycle arrest
- cell death
- endoplasmic reticulum stress
- pi k akt
- fluorescent probe