The influence of proline isomerization on potency and stability of anti-HIV antibody 10E8.

ABSTRACT: Monoclonal antibody (mAb) 10E8 recognizes a highly conserved epitope on HIV and is capable of neutralizing > 95% of circulating viral isolates making it one of the most promising Abs against HIV. Solution instability and biochemical heterogeneity of 10E8 has hampered its development for clinical use. We identify the source of 10E8 heterogeneity being linked to cis/trans isomerization at two prolines within the YPP motif in the CRD3 loop that exists as two predominant conformers that interconvert on a slow timescale. The Y_transP conformation conformer can bind the HIV gp41 epitope, while the Y_cisP is not binding competent and shows a higher aggregation propensity. The high barrier of isomerization and propensity to adopt non-binding competent proline conformers provide

SUBMITTER: Guttman M 

PROVIDER: S-EPMC7458915 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature