Role of two conserved glycine residues in the β-propeller domain of the integrin α4 subunit in VLA-4 conformation and function

The N-terminal region of the alpha integrin subunits is predicted to fold 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 recognition of alpha 4 by anti-alpha 4 antibodies which map to the beta-propeller, The improper alpha 4 conformation also led to an altered association with the beta 1 subunit, and to a lack of alpha 4 beta 1 adhesion 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 conservation of Gly(130) and Gly(190) among integrin alpha subunits suggests 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.