Native Conformation and Canonical Disulfide Bond Formation Are Interlinked Properties of HIV-1 Env Glycoproteins
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Issue Date
2016-03Author
Go, Eden P.
Cupo, Albert
Ringe, Rajesh P.
Pugach, Pavel
Moore, John P.
Desaire, Heather
Publisher
Science Publications
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
Copyright © 2016, American Society for Microbiology
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Show full item recordAbstract
We investigated whether there is any association between a native-like conformation and the presence of only the canonical (i.e., native) disulfide bonds in the gp120 subunits of a soluble recombinant human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein. We used a mass spectrometry (MS)-based method to map the disulfide bonds present in nonnative uncleaved gp140 proteins and native-like SOSIP.664 trimers based on the BG505 env gene. Our results show that uncleaved gp140 proteins were not homogeneous, in that substantial subpopulations (20 to 80%) contained aberrant disulfide bonds. In contrast, the gp120 subunits of the native-like SOSIP.664 trimer almost exclusively retained the canonical disulfide bond pattern. We also observed that the purification method could influence the proportion of an Env protein population that contained aberrant disulfide bonds. We infer that gp140 proteins may always contain a variable but substantial proportion of aberrant disulfide bonds but that the impact of this problem can be minimized via design and/or purification strategies that yield native-like trimers. The same factors may also be relevant to the production and purification of monomeric gp120 proteins that are free of aberrant disulfide bonds.
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Citation
Go EP, Cupo A, Ringe R, Pugach P, Moore JP, Desaire H. 2016. Native conformation and canonical disulfide bond formation are interlinked properties of HIV-1 Env glycoproteins. J Virol 90:2884 –2894. doi:10.1128/JVI.01953-15.
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