ROLE OF 2 CONSERVED GLYCINE RESIDUES IN THE BETA-PROPELLER DOMAIN OF THE INTEGRIN ALPHA-4 SUBUNIT IN VLA-4 CONFORMATION AND FUNCTION

The N-terminal region of the alpha integrin subunits is predicted to f old into a beta-propeller domain. Using K562 alpha 4 transfectants we show that mutations at alpha 4 subunit residues Gly(130) and Gly(190) affect the conformation of this domain causing a reduction in the reco gnition of alpha 4 by anti-alpha 4 antibodies which map to the beta-pr opeller, The improper alpha 4 conformation also led to an altered asso ciation with the beta 1 subunit, and to a lack of alpha 4 beta 1 adhes ion to VCAM-1 and CS-1/fibronectin, as well as an abolishment of anti- alpha 4- and anti-beta 1-dependent homotypic aggregation. The total co nservation of Gly(130) and Gly(190) among integrin alpha subunits sugg ests their importance in the correct folding of their respective beta- propeller domains, and thus, in the adhesive activity of the integrins , (C) 1998 Federation of European Biochemical Societies.