Role of two conserved glycine residues in the beta-propeller domain of the integrin alpha4 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 alpha4 transfectants we show that mutations at alpha4 subunit residues Gly130 and Gly190 affect the conformation of this domain causing a reduction in the recognition of alpha4 by anti-alpha4 antibodies which map to the beta-propeller. The improper alpha4 conformation also led to an altered association with the beta1 subunit, and to a lack of alpha4beta1 adhesion to VCAM-1 and CS-1/fibronectin, as well as an abolishment of anti-alpha4- and anti-beta1-dependent homotypic aggregation. The total conservation of Gly130 and Gly190 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.
Guerrero-Esteo
M
M
Centro de Investigaciones Biológicas, Departamento de Immunología, Velázquez, Madrid, Spain.
Ruiz-Velasco
N
N
Muñoz
M
M
Teixidó
J
J
D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D005998:Glycine / Q000502:physiology*; D006801:Humans; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D016023:Integrins / Q000737:chemistry* / Q000502:physiology; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017510:Protein Folding; D016201:Receptors, Lymphocyte Homing / Q000737:chemistry* / Q000502:physiology; D014162:Transfection
D015703:Antigens, CD; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D039441:Integrin alpha4; D005998:Glycine