A point mutation of integrin β₂ subunit blocks binding of α₅β₁ to fibronectin and invasin but not recruitment to adhesion plaques

A point mutation in a highly conserved region of the β₁ subunit, Asp¹³⁰ to Ala (D130A) substitution, abrogates the Arg-Gly-Asp (RGD)-dependent binding of α₅β₁ to fibronectin (FN) without disrupting gross structure or heterodimer assembly. The D130A mutation also interferes with binding to invasin, a ligand that lacks RGD sequence. In spite of the lack of detectable FN binding by α₅β₁(D130A), it was recruited to adhesion plaques formed on FN by endogenous hamster receptors. Thus, intact ligand binding function is not required for recruitment of α₅β₁ to adhesion plaques. Overexpression of β₁(D130A) partially interfered with endogenous α₅β₁ function, thus defining a dominant negative β₁ integrin mutation.