Sub-Nanometer Structures of HIV-1 Envelope Trimers on Aldrithiol-2 Inactivated Virus Particles
| Autor: | Walther Mothes, Baoshan Zhang, Peter D. Kwong, Wenwei Li, Julian W. Bess, Ze Li, Cara W. Chao, Jason Gorman, Maolin Lu, Jeffrey D. Lifson, Jun Liu, Tongqing Zhou, Daniel S. Terry, Scott C. Blanchard |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Electron Microscope Tomography Protein Conformation viruses Trimer HIV Infections HIV Envelope Protein gp120 Gp41 Virus Article law.invention Cell Line 03 medical and health sciences 0302 clinical medicine 2 2'-Dipyridyl Structural Biology Viral entry law Humans Disulfides Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences Chemistry Cryoelectron Microscopy Virion virus diseases Oxidants HIV Envelope Protein gp41 Membrane Solubility Helix Biophysics Recombinant DNA HIV-1 Protein Multimerization Glycoprotein 030217 neurology & neurosurgery |
| Zdroj: | Nat Struct Mol Biol |
| Popis: | The HIV-1 envelope glycoprotein (Env) trimer, composed of gp120 and gp41 subunits, mediates viral entry into cells. Recombinant Env trimers have been studied structurally, but characterization of Env embedded in intact virus membranes has been limited to low resolution. Here, we deploy cryo-electron tomography and subtomogram averaging to determine the structures of Env trimers on aldrithiol-2 (AT-2)-inactivated virions in ligand-free, antibody-bound and CD4-bound forms at subnanometer resolution. Tomographic reconstructions document molecular features consistent with high-resolution structures of engineered soluble and detergent-solubilized Env trimers. One of three conformational states previously predicted by smFRET was not observed by cryo-ET, potentially owing to AT-2 inactivation. We did observe Env trimers to open in situ in response to CD4 binding, with an outward movement of gp120-variable loops and an extension of a critical gp41 helix. Overall features of Env trimer embedded in AT-2-treated virions appear well-represented by current engineered trimers. Cryo-ET and subtomogram averaging analyses are used to determine structures of HIV-1 Env trimers on the surface of inactivated virions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|