For catch bonds, it all hinges on the interdomain region

Abstract

Tensile mechanical force was long assumed to increase the detachment rates of biological adhesive bonds (Bell, 1978). However, in the last few years, several receptor-ligand pairs were shown to form "catch bonds," whose lifetimes are enhanced by moderate amounts of force. These include the bacterial adhesive protein FimH binding to its ligand mannose (Thomas et al., 2002; Thomas et al., 2006), blood cell adhesion proteins P- and L-selectin binding to sialyl Lewis X (sLe(X))-containing ligands (Marshall et al., 2003; Evans et al., 2004; Sarangapani et al., 2004), and the myosin-actin motor protein interaction (Guo and Guilford, 2006). The structural mechanism behind this counterintuitive force-enhanced catch bond behavior is of great interest.

Figure 1.

Conformational changes in P-selectin. P-selectin was cocrystalized with (purple) and without (gold) the PSGL-1 ligand (peptide, blue; sLe^X, cyan). The two structures differ in a series of changes that span from the binding site to the hinge region, indicated by the arrow. Residue 30 is shown in green, with the position of the wedge mutant glycosylation shown as a green circle. Shown in red is residue N138 forming a hydrogen bond with Y37 as they appear in the unliganded L-selectin structure, which is nearly identical in conformation to unliganded P-selectin.