title: Folding of the beta-propeller domain of the integrin alphaL subunit is independent of the I domain and dependent on the beta2 subunit.
abstract: 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.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.forename: T A
authors.initials: TA
authors.lastname: Springer
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D018821:CD18 Antigens / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D002461:Cell Line, Transformed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D017510:Protein Folding
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1