PBIO SEMINAR SERIES

Activation of the bacterial adhesive protein FimH by mechanical force.

Wednesday - March 15, 2006
05-06 SEMINAR SERIES

Wendy Thomas
Assistant Professor of Bioengineering University of Washington
Speaker's website

Host: Chip Asbury

Like voltage-sensitive channels and motor proteins, some adhesive proteins act at the interface between biological signals and physical signals. The bacterial adhesive protein FimH binds to mannose-containing glycoproteins in flowing bodily fluids and thus is subjected to substantial mechanical force. While it is generally expected that this would wash bacteria off tissues, high fluid flow rates enhance adhesion of/ Escherichia coli/ bacteria when it is mediated by the adhesive protein FimH. This occurs as bacteria switch from transient to rolling to stationary adhesion. To measure the lifetime of individual FimH-mannose bonds in the presence of mechanical force, we use parallel plate flow chambers and beads with low concentrations of mannose and FimH. These experiments strongly suggest that the bond can exist in two states with very different lifetimes, and that mechanical force favors the long-lived state. Thus, FimH is a catch bond (a bond that is longer lived under tensile mechanical force). Using biochemical, molecular biology, and structural simulation techniques, we and our collaborators demonstrate that FimH has a regulatory domain that inhibits the activity of the binding domain unless the interaction is removed by mechanical force or mutations in the structure of FimH. This concept of inter-domain regulation provides a mechanism for transduction of a mechanical to a chemical signal.