HIV-1 Envelope and MPER Antibody Structures in Lipid Assemblies.
Cell Rep
; 31(4): 107583, 2020 04 28.
Article
in En
| MEDLINE
| ID: mdl-32348769
ABSTRACT
Structural and functional studies of HIV envelope glycoprotein (Env) as a transmembrane protein have long been complicated by challenges associated with inherent flexibility of the molecule and the membrane-embedded hydrophobic regions. Here, we present approaches for incorporating full-length, wild-type HIV-1 Env, as well as C-terminally truncated and stabilized versions, into lipid assemblies, providing a modular platform for Env structural studies by single particle electron microscopy. We reconstitute a full-length Env clone into a nanodisc, complex it with a membrane-proximal external region (MPER) targeting antibody 10E8, and structurally define the full quaternary epitope of 10E8 consisting of lipid, MPER, and ectodomain contacts. By aligning this and other Env-MPER antibody complex reconstructions with the lipid bilayer, we observe evidence of Env tilting as part of the neutralization mechanism for MPER-targeting antibodies. We also adapt the platform toward vaccine design purposes by introducing stabilizing mutations that allow purification of unliganded Env with a peptidisc scaffold.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
HIV Envelope Protein gp41
/
HIV-1
/
Lipid Bilayers
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2020
Document type:
Article
Affiliation country: