Folding of the beta-propeller domain of the integrin alphaL subunit is independent of the I domain and dependent on the beta2 subunit.

We have studied the folding during biosynthesis of the lymphocyte function-associated antigen 1 (LFA-1) alphaL subunit using mAb to epitopes that map to seven different regions within the amino acid sequence. The N-terminal portion of alphaL is predicted to contain a beta-propeller domain, consisting of seven beta-sheets, and an I domain that is predicted to be inserted between beta-sheet 2 and beta-sheet 3 of the beta-propeller. The I domain of alphaL folds before association with the beta2 subunit, as shown by immunoprecipitation of the unassociated alphaL subunit by mAbs specific for four different sequence elements within the I domain. By contrast, the beta-propeller domain is not folded in unassociated alphaL after a chase of as long as 12 h after synthesis, but does fold upon association with beta2. This is shown with mAbs to regions of alphaL, 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 beta-propeller domain suggests that this region is partially folded before subunit association. The results show that the I domain and beta-propeller domains fold independently of one another, and suggest that the beta-propeller domain bears an interface for association with the beta subunit.