Saturation Mutagenesis of the HIV-1 Envelope CD4 Binding Loop Reveals Residues Controlling Distinct Trimer Conformations
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Program in Molecular Medicine
Document TypeJournal Article
KeywordsBiochemistry, Biophysics, and Structural Biology
Immunology and Infectious Disease
MetadataShow full item record
AbstractThe conformation of HIV-1 envelope (Env) glycoprotein trimers is key in ensuring protection against waves of neutralizing antibodies generated during infection, while maintaining sufficient exposure of the CD4 binding site (CD4bs) for viral entry. The CD4 binding loop on Env is an early contact site for CD4 while penetration of a proximal cavity by CD4 triggers Env conformational changes for entry. The role of residues in the CD4 binding loop in regulating the conformation of the trimer and trimer association domain (TAD) was investigated using a novel saturation mutagenesis approach. Single mutations identified, resulted in distinct trimer conformations affecting CD4bs exposure, the glycan shield and the TAD across diverse HIV-1 clades. Importantly, mutations that improve access to the CD4bs without exposing the immunodominant V3 loop were identified. The different trimer conformations identified will affect the specificity and breadth of nabs elicited in vivo and are important to consider in design of Env immunogens for vaccines.
SourcePLoS Pathog. 2016 Nov 7;12(11):e1005988. doi: 10.1371/journal.ppat.1005988. eCollection 2016. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40199
Related ResourcesLink to Article in PubMed
RightsCopyright: © 2016 Duenas-Decamp et al.
Except where otherwise noted, this item's license is described as Copyright: © 2016 Duenas-Decamp et al.