Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation
Abstract
Trimeric forms of HIV-1 envelope glycoproteins are being used for structural and vaccine studies. The most common way to make these proteins is to eliminate the cleavage site between the glycoprotein (gp)120 and gp41 subunits. We show that doing so creates trimers that adopt irregular, nonnative configurations. Cleaved, stabilized trimers, in contrast, resemble the native spikes on the HIV-1 virus. Our findings will help structural and vaccine programs by showing how to make native-like trimers. The rationale for vaccine trials based on the use of uncleaved gp140 trimers should be reevaluated.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- November 2013
- DOI:
- 10.1073/pnas.1314351110
- Bibcode:
- 2013PNAS..11018256R