The impact of proline isomerization on antigen binding and the analytical profile of a trispecific anti-HIV antibody.

ABSTRACT: Proline cis-trans conformational isomerization is a mechanism that affects different types of protein functions and behaviors. Using analytical characterization, structural analysis, and molecular dynamics simulations, we studied the causes of an aberrant two-peak size-exclusion chromatography profile observed for a trispecific anti-HIV antibody. We found that proline isomerization in the tyrosine-proline-proline (YPP) motif in the heavy chain complementarity-determining region (CDR)3 domain of one of the antibody arms (10e8v4) was a component of this profile. The pH effect on the conformational equilibrium that led to these two populations was presumably caused by a histidine residue (H147) in the light chain that is in direct contact with the YPP motif. Finally, we demonstrated th

SUBMITTER: Masiero A 

PROVIDER: S-EPMC8675452 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature