title: Direct extracellular contact between integrin alpha(3)beta(1) and TM4SF protein CD151.
abstract: Previously we established that the alpha(3)beta(1) integrin shows stable, specific, and stoichiometric association with the TM4SF (tetraspannin) protein CD151. Here we used a membrane impermeable cross-linking agent to show a direct association between extracellular domains of alpha(3)beta(1) and CD151. The alpha(3)beta(1)-CD151 association site was then mapped using chimeric alpha(6)/alpha(3) integrins and CD151/NAG2 TM4SF proteins. Complex formation required an extracellular alpha(3) site (amino acids (aa) 570-705) not previously known to be involved in specific integrin contacts with other proteins and a region (aa 186-217) within the large extracellular loop of CD151. Notably, the anti-CD151 monoclonal antibody TS151r binding epitope, previously implicated in alpha(3) integrin association, was mapped to the same region of CD151 (aa 186-217). Finally, we demonstrated that both NH(2)- and COOH-terminal domains of CD151 are located on the inside of the plasma membrane, thus confirming a long suspected model of TM4SF protein topology.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Yauch
authors.forename: A R
authors.initials: AR
authors.lastname: Kazarov
authors.forename: B
authors.initials: B
authors.lastname: Desai
authors.forename: R T
authors.initials: RT
authors.lastname: Lee
authors.forename: M E
authors.initials: ME
authors.lastname: Hemler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D005110:Extracellular Space; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D060185:Tetraspanin 24
chemical_list: D015703:Antigens, CD; C554715:CD151 protein, human; D039201:Integrin alpha3beta1; D016023:Integrins; D060185:Tetraspanin 24