The C-type lectin domain of CD62P (P-selectin) functions as an integrin ligand

Recognition of integrins by CD62P has not been reported and this motivated a docking simulation using integrin av133 as a target. We predicted that the C-type lectin domain of CD62P functions as a potential integrin ligand and observed that it specifically bound to soluble 133 and 131 integrins. Known inhibitors of the interaction between CD62P-PSGL-1 did not suppress the binding, whereas the disintegrin domain of ADAM-15, a known integrin ligand, suppressed recognition by the lectin domain. Furthermore, an R16E/ K17E mutation in the predicted integrin-binding interface located outside of the glycan-binding site within the lectin domain, strongly inhibited CD62P binding to integrins. In contrast, the E88D mutation that strongly disrupts glycan binding only slightly affected CD62Pintegrin recognition, indicating that the glycan and integrin-binding sites are distinct. Notably, the lectin domain allosterically activated integrins by binding to the allosteric site 2. We conclude that CD62Pintegrin binding may function to promote a diverse set of cell-cell adhesive interactions given that 133 and 131 integrins are more widely expressed than PSGL-1 that is limited to leukocytes.

Automated summary

Recognition of integrins by CD62P has been discovered, and the C-type lectin domain of CD62P functions as a potential integrin ligand. The binding between CD62P and soluble 133 and 131 integrins is specifically observed. Inhibitors of CD62P-PSGL-1 interaction do not affect this binding, while the disintegrin domain of ADAM-15, another integrin ligand, can suppress recognition by the lectin domain. A mutation in the predicted integrin-binding interface strongly inhibits CD62P binding to integrins, and the glycan and integrin-binding sites are distinct. The lectin domain of CD62P can also allosterically activate integrins.