PT  - JOURNAL ARTICLE
AU  - Takada, Yoko K
AU  - Simon, Scott I
AU  - Takada, Yoshikazu
TI  - The C-type lectin domain of CD62P (P-selectin) functions as an integrin ligand
AID  - 10.26508/lsa.202201747
DP  - 2023 Jul 01
TA  - Life Science Alliance
PG  - e202201747
VI  - 6
IP  - 7
4099  - http://www.life-science-alliance.org/content/6/7/e202201747.short
4100  - http://www.life-science-alliance.org/content/6/7/e202201747.full
SO  - Life Sci. Alliance2023 Jul 01; 6
AB  - Recognition of integrins by CD62P has not been reported and this motivated a docking simulation using integrin αvβ3 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 β3 and β1 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 CD62P-integrin 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 CD62P-integrin binding may function to promote a diverse set of cell–cell adhesive interactions given that β3 and β1 integrins are more widely expressed than PSGL-1 that is limited to leukocytes.