Integrin-like allosteric properties of the catch bond-forming FimH adhesin of Escherichia coli.
FimH is the adhesive subunit of type 1 fimbriae of the Escherichia coli that is composed of a mannose-binding lectin domain and a fimbria-incorporating pilin domain. FimH is able to interact with mannosylated surface via a shear-enhanced catch bond mechanism. We show that the FimH lectin domain possesses a ligand-induced binding site (LIBS), a type of allosterically regulated epitopes characterized in integrins. Analogous to integrins, in FimH the LIBS epitope becomes exposed in the presence of the ligand (or "activating" mutations) and is located far from the ligand-binding site, close to the interdomain interface. Also, the antibody binding to the LIBS shifts adhesin from the low to high affinity state. Binding of streptavidin to the biotinylated residue within the LIBS also locks FimH in the high affinity state, suggesting that the allosteric perturbations in FimH are sustained by the interdomain wedging. In the presence of antibodies, the strength of bacterial adhesion to mannose is increased similar to the increase observed under shear force, suggesting the same allosteric mechanism, a shift in the interdomain configuration. Thus, an integrin-like allosteric link between the binding pocket and the interdomain conformation can serve as the basis for the catch bond property of FimH and, possibly, other adhesive proteins.
Tchesnokova
Veronika
V
Department of Microbiology, University of Washington, Seattle, Washington 98105, USA.
Aprikian
Pavel
P
Yakovenko
Olga
O
Larock
Christopher
C
Kidd
Brian
B
Vogel
Viola
V
Thomas
Wendy
W
Sokurenko
Evgeni
E
D018830:Adhesins, Escherichia coli / Q000235:genetics / Q000378:metabolism*; D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000907:Antibodies, Bacterial / Q000737:chemistry / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D048168:Escherichia coli K12 / Q000235:genetics / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000502:physiology
D018830:Adhesins, Escherichia coli; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000939:Epitopes; D008024:Ligands; D037601:Mannose-Binding Lectin; C058769:fimH protein, E coli; D036781:Fimbriae Proteins