Allosteric coupling in the bacterial adhesive protein FimH

摘要: The protein FimH is expressed by the majority of commensal and uropathogenic strains Escherichia coli on tips type 1 fimbriae mediates adhesion via a catch bond to its ligand mannose. Crystal structures show an allosteric conformational change, but it remains unclear whether all observed structural differences are part mechanism. Here we use analysis tool RosettaDesign combined with human insight identify synthesize 10 mutations in four regions that predicted would stabilize one conformations region. function each variant was characterized measuring binding mannose, whereas state determined using conformation-specific monoclonal antibody. These studies demonstrated region investigated indeed However, strongly suggested some were more tightly coupled mannose others antibody binding. In addition, identified many variants appear locked low affinity state. Knowledge regulatory sites outside active effector as well ability make may be crucial future development novel antiadhesive antimicrobial therapies regulation inhibit FimH. Background: bacterial adhesin allosterically regulated. Results: Mutations designed control created or high predicted. Conclusion: Three together, site weakly those regions. Significance: Allosteric can used develop for infections.