Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability

Leopold Kong, Linling He, Natalia de Val, Nemil Vora, Charles D. Morris, Parisa Azadnia, Devin Sok, Bin Zhou, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson () and Jiang Zhu ()
Additional contact information
Leopold Kong: The Scripps Research Institute
Linling He: The Scripps Research Institute
Natalia de Val: The Scripps Research Institute
Nemil Vora: The Scripps Research Institute
Charles D. Morris: The Scripps Research Institute
Parisa Azadnia: The Scripps Research Institute
Devin Sok: International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute
Bin Zhou: The Scripps Research Institute
Dennis R. Burton: International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute
Andrew B. Ward: The Scripps Research Institute
Ian A. Wilson: The Scripps Research Institute
Jiang Zhu: The Scripps Research Institute

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract The trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and neutralization. Despite advances in trimer design, the roots of Env trimer metastability remain elusive. Here we investigate the contribution of two Env regions to metastability. First, we computationally redesign a largely disordered bend in heptad region 1 (HR1) of SOSIP trimers that connects the long, central HR1 helix to the fusion peptide, substantially improving the yield of soluble, well-folded trimers. Structural and antigenic analyses of two distinct HR1 redesigns confirm that redesigned Env closely mimics the native, prefusion trimer with a more stable gp41. Next, we replace the cleavage site between gp120 and gp41 with various linkers in the context of an HR1 redesign. Electron microscopy reveals a potential fusion intermediate state for uncleaved trimers containing short but not long linkers. Together, these results outline a general approach for stabilization of Env trimers from diverse HIV-1 strains.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/ncomms12040 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12040

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms12040

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().