Abstract
Author SummaryNoncovalent biological interactions are commonly subjected to mechanical force, particularly when they are involved in adhesion or cytoskeletal movements. While one might expect mechanical force to break these interactions, some of them form so-called catch bonds that lock on harder under force, like a nanoscale finger-trap. In this study, we show that the catch-bond forming adhesive protein FimH, which is located at the tip of E. coli fimbriae, allows bacteria to bind to urinary epithelial cells in a shear-dependent manner; that is, they bind at high but not at low flow. We show that isolated fimbrial tips, consisting of elongated protein complexes with FimH at the apex, reproduce this behavior in vitro. Our molecular dynamics simulations of the fimbrial tip structure show that FimH is shaped like a hook that is normally rigid but opens under force, causing structural changes that lead to firm anchoring of the bacteria on the surface. In contrast, the more distal adaptor proteins of the fimbrial tip create a flexible connection of FimH to the rigid fimbria, enhancing the ability of the adhesin to move into position and form bonds with mannose on the surface. We suggest that the entire tip complex forms a hook-chain, ideal for rapid and stable anchoring in flow.
Highlights
Most adhesive biological processes are exposed to mechanical stress resulting from fluid flow-induced shear
Noncovalent biological interactions are commonly subjected to mechanical force, when they are involved in adhesion or cytoskeletal movements
We show that the catch-bond forming adhesive protein FimH, which is located at the tip of E. coli fimbriae, allows bacteria to bind to urinary epithelial cells in a shear-dependent manner; that is, they bind at high but not at low flow
Summary
Most adhesive biological processes are exposed to mechanical stress resulting from fluid flow-induced shear. In the case of gramnegative bacterial cells, the interaction with the host tissue is known to be mediated by adhesive proteins (adhesins) that are, in many cases, positioned at the tip of multimeric hair-like appendages called fimbriae (or pili) and bind to receptor molecules on the target cells or tissues [1,2]. The 30 kDa FimH protein is the most common, mannose-specific adhesin of Escherichia coli located on the tip of type 1 fimbriae [3,4]. Bacterial adhesion mediated by type 1 fimbriae is enhanced by shear stress [5,6], and single molecule force spectroscopy experiments have shown that a tensile force extends the lifetime of the bond between FimH and the mannose receptor [7]. The force-enhanced, so-called catch bond mechanism of FimH binding involves allosteric activation of the mannose-binding lectin domain (Ld), which switches from a low- to a high-affinity conformation upon separation from the anchoring pilin domain (Pd)
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