Folding of the β-propeller domain of the integrin α(L) subunit is independent of the I domain and dependent on the β(2) subunit

We have studied the folding during biosynthesis of the lymphocyte function-associated antigen 1 (LFA-1) α(L) subunit using mAb to epitopes that map to seven different regions within the amino acid sequence. The N-terminal portion of α(L) is predicted to contain a β-propeller domain, consisting of seven β-sheets, and an I domain that is predicted to be inserted between β-sheet 2 and β-sheet 3 of the β-propeller. The I domain of α(L) folds before association with the β(2) subunit, as shown by immunoprecipitation of the unassociated α(L) subunit by mAbs specific for four different sequence elements within the I domain. By contrast, the β-propeller domain is not folded in unassociated α(L) after a chase of as long as 12 h after synthesis, but does fold upon association with β(2). This is shown with mAbs to regions of α(L), that precede and follow the I domain in the primary structure. A mAb that maps near the junction of the C terminus of the I domain with the β-propeller domain suggests that this region is partially folded before subunit association. The results show that the I domain and β-propeller domains fold independently of one another, and suggest that the β-propeller domain bears an interface for association with the β subunit.