Oligomerization of the integrin alpha llb beta 3: Roles of the transmembrane and cytoplasmic domains

Integrins are a family of alpha/beta heterodimeric membrane proteins, which mediate cell-cell and cell-matrix interactions. The molecular mechanisms b y which integrins are activated and cluster are currently poorly understood . One hypothesis posits that the cytoplasmic tails of the alpha and beta su bunits interact strongly with one another in a 1:1 interaction, and that th is interaction is modulated in the course of the activation of alpha IIb be ta3 [Hughes, P. E., et al. (1996) J. Biol. Chem. 271, 6571-6574]. To examin e the structural basis for this interaction, protein fragments encompassing the transmembrane elix plus cytoplasmic tails of the alpha and beta subuni ts of alpha IIb beta3 were expressed and studied in phospholipid micelles a t physiological salt concentrations. Analyses of these fragments by analyti cal ultracentrifugation, NMR, circular dichroism, and electrophoresis indic ated that they had very little or no tendency to interact with one another. Instead, they formed homomeric interactions, with the alpha- and beta -fra gments forming dimers and trimers, respectively. Thus, these regions of the protein structure may contribute to the clustering of integrins that accom panies cellular adhesion.