title: Role of two conserved glycine residues in the beta-propeller domain of the integrin alpha4 subunit in VLA-4 conformation and function.
abstract: 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.
authors.affiliation: Centro de Investigaciones Biológicas, Departamento de Immunología, Velázquez, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Guerrero-Esteo
authors.forename: N
authors.initials: N
authors.lastname: Ruiz-Velasco
authors.forename: M
authors.initials: M
authors.lastname: Muñoz
authors.forename: J
authors.initials: J
authors.lastname: Teixidó
mesh_terms: 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
chemical_list: D015703:Antigens, CD; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D039441:Integrin alpha4; D005998:Glycine