Toggle switch residues control allosteric transitions in bacterial adhesins by participating in a concerted repacking of the protein core.

ABSTRACT: Critical molecular events that control conformational transitions in most allosteric proteins are ill-defined. The mannose-specific FimH protein of Escherichia coli is a prototypic bacterial adhesin that switches from an 'inactive' low-affinity state (LAS) to an 'active' high-affinity state (HAS) conformation allosterically upon mannose binding and mediates shear-dependent catch bond adhesion. Here we identify a novel type of antibody that acts as a kinetic trap and prevents the transition between conformations in both directions. Disruption of the allosteric transitions significantly slows FimH's ability to associate with mannose and blocks bacterial adhesion under dynamic conditions. FimH residues critical for antibody binding form a compact epitope that is located away from the mannose-

SUBMITTER: Kisiela DI 

PROVIDER: S-EPMC8064603 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature