Folding of the conserved domain but not of flanking regions in the integrin beta(2) subunit requires association with the alpha subunit

We have used immunoprecipitation with mAbs to probe folding during biosynthesis of the beta(2) integrin subunit of lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) before and after association with the alpha(L) subunit, An evolutionarily conserved region is present in the beta(2) subunit between amino acid residues 102 and 344, mAbs to one subregion before the conserved region, and two subregions after the conserved domain, immunoprecipitated both the unassociated beta(2)' precursor and mature alpha(L)/beta(2) complex, suggesting portions of these subregions are folded before association with alpha(L). An activating mAb to the C-terminal cysteine-rich region, KIM127, preferentially bound to the unassociated beta subunit, suggesting that it may bind to an epitope that is in an alpha beta interface in unactivated LFA-1. By contrast, mAbs to five different epitopes in the conserved region did not react with unassociated beta(2)' precursor, suggesting that this region folds after alpha(L) association and is intimately associated with the alpha(L) subunit in the alpha(L)/beta(2) complex. mAbs to two different epitopes that involve the border between the conserved region and the C-terminal segment, were fully or partially reactive with the beta(2)' precursor, suggesting that this region is partially folded before association with alpha(L). The findings suggest that the conserved region is a distinct folding and hence structural unit, and is intimately associated with the alpha subunit.