The CD9, CD81, and CD151 EC2 domains bind to the classical RGD-binding site of integrin αvβ3

Abstract

Tetraspanins play important roles in normal (e.g. cell adhesion, motility, activation, and proliferation) and pathological conditions (e.g. metastasis and viral infection). Tetraspanins interact with integrins and regulate integrin functions, but the specifics of tetraspanin-integrin interactions are unclear. Using co-immunoprecipitation with integrins as a sole method to detect interaction between integrins and full-length tetraspanins, it has been proposed that the variable region (helices D and E) of the extracellular-2 (EC2) domain of tetraspanins laterally associates with a non-ligand-binding site of integrins. We describe that, using adhesion assays, the EC2 domain of CD81, CD9, and CD151 bound to integrin αvβ3, and this binding was suppressed by cRGDfV, a specific inhibitor of αvβ3, and antibody 7E3, which is mapped to the ligand-binding site of β3. We also present evidence that the specificity loop of β3 directly bound to the EC2 domains. This suggests that the EC2 domains specifically bind to the classical ligand-binding site of αvβ3. αvβ3 was a more effective receptor for the EC2 domains than the previously known tetraspanin receptors α3β1, α4β1, and α6β1. Docking simulation predicted that the helices A and B of CD81 EC2 bind to the RGD-binding site of αvβ3. Substituting Lys residues at positions 116 and 144/148 of CD81 EC2 in the predicted integrin-binding interface reduced the binding of CD81 EC2 to αvβ3, consistent with the docking model. These findings suggest that, in contrast with previous models, the ligand-binding site of integrin αvβ3, a new tetraspanin receptor, binds to the constant region (helices A and B) of the EC2 domain.

CD151 promotes cell metastasis via activating TGF-β1/Smad signaling in renal cell carcinoma

“…CD151 can also interact with other tetraspanin family members (e.g. CD9, CD81) and integrins to regulate migration, adhesion and signaling of cells [ 26 , 27 ].…”

Direct observation of condensate and vortex confinement in nanostructured superconductors

“…Confinement effects play an important role in different physical phenomena especially in quantum systems like Bose-Einstein condensates, superconductors, and superfluids. For example, the ability to structure superconducting devices at length scales comparable to the characteristic sizes (penetration dept λ and coherence length ξ ) of the condensate revealed a vast world of possibilities to explore quantum phenomena (e.g., creation of artificial atoms [1], induction of quantum phase slip lines [2], confinement effects [3], to name a few). In the latter example, theoretical modeling of these systems solving the Ginzburg-Landau (G-L) [4,5] or Bogoliubov-deGennes (B-dG) [6] equations for single and/or multiband mesoscopic superconductors has been done.…”

Anti-GPR56 monoclonal antibody potentiates GPR56-mediated Src-Fak signaling to modulate cell adhesion

“…Interestingly, Jeong et al demonstrated synergistic activities of GPR56 and α3β1 integrin during cerebral cortical development (34), which may account for GPR56 activation of integrin partners such as Src-Fak. Additionally, GPR56-interacting proteins including CD81 and collagen III (24,35) have also been shown to associate with integrins (36)(37)(38). The STP region overlaps with the PLL domain which shares sequence similarity to LNS domains which can mediate cell adhesion (19,39).…”