Beyond induced-fit receptor-ligand interactions: structural changes that can significantly extend bond lifetimes.
While the lifetime of conventional receptor-ligand interactions is shortened by tensile mechanical force, some recently discovered interactions, termed catch bonds, can be strengthened by force. Motivated by the search for the underpinning structural mechanisms, we here explore the structural dynamics of the binding site of the bacterial adhesive protein FimH by molecular dynamics and steered molecular dynamics. While the crystal structure of only one FimH conformation has been reported so far, we describe two distinctively different conformations of the mannose-bound FimH binding site. Force-induced dissociation was slowed when the mannose ring rotated such that additional force-bearing hydrogen bonds formed with the base of the FimH binding pocket. The lifetime of the complex was further enhanced significantly by rigidifying this base. We finally show how even sub-angstrom spatial alterations of the hydrogen bonding pattern within the base can lead to significantly decreased bond lifetimes.
Nilsson
Lina M
LM
Department of Materials, ETH Zürich, Wolfgang-Pauli-Strasse 10, HCI F443, CH-8093 Zürich, Switzerland.
Thomas
Wendy E
WE
Sokurenko
Evgeni V
EV
Vogel
Viola
V
D018830:Adhesins, Escherichia coli / Q000737:chemistry*; D001665:Binding Sites; D001696:Biomechanical Phenomena; D036781:Fimbriae Proteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D008358:Mannose / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014867:Water / Q000737:chemistry
D018830:Adhesins, Escherichia coli; D008024:Ligands; C058769:fimH protein, E coli; D014867:Water; D036781:Fimbriae Proteins; D008358:Mannose