Flipping the switch from monomeric to dimeric CV-N has little effect on antiviral activity.
Cyanovirin-N can exist in solution in monomeric and domain-swapped dimeric forms, with HIV-antiviral activity being reported for both. Here we present results for CV-N variants that form stable solution dimers: the obligate dimer [DeltaQ50]CV-N and the preferential dimer [S52P]CV-N. These variants exhibit comparable DeltaG values (10.6 +/- 0.5 and 9.4 +/- 0.5 kcal.mol(-1), respectively), similar to that of stabilized, monomeric [P51G]CV-N (9.8 +/- 0.5 kcal.mol(-1)), but significantly higher than wild-type CV-N (4.1 +/- 0.2 kcal.mol(-1)). During folding/unfolding, no stably folded monomer was observed under any condition for the obligate dimer [DeltaQ50]CV-N, whereas two monomeric, metastable species were detected for [S52P]CV-N at low concentrations. This is in contrast to our previous results for [P51G]CV-N and wild-type CV-N, for which the dimeric forms were found to be the metastable species. The dimeric mutants exhibit comparable antiviral activity against HIV and Ebola, similar to that of wild-type CV-N and the stabilized [P51G]CV-N variant.
Barrientos
Laura G
LG
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. lbarrientos1@cdc.gov
Lasala
Fátima
F
Delgado
Rafael
R
Sanchez
Anthony
A
Gronenborn
Angela M
AM
D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D001681:Biological Assay; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D019281:Dimerization; D029043:Ebolavirus / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; C107733:cyanovirin N