title: Structural basis of integrin transmembrane activation.
abstract: Integrins are cell adhesion receptors that transmit bidirectional signals across plasma membrane and are crucial for many biological functions. Recent structural studies of integrin transmembrane (TM) and cytoplasmic domains have shed light on their conformational changes during integrin activation. A structure of the resting state was solved based on Rosetta computational modeling and experimental data using intact integrins on mammalian cell surface. In this structure, the alpha(IIb) GXXXG motif and their beta(3) counterparts of the TM domains associate with ridge-in-groove packing, and the alpha(IIb) GFFKR motif and the beta(3) Lys-716 in the cytoplasmic segments play a critical role in the alpha/beta association. Comparing this structure with the NMR structures of the monomeric alpha(IIb) and beta(3) (represented as active conformations), the alpha subunit helix remains similar after dissociation whereas beta subunit helix is tilted by embedding additional 5-6 residues into the lipid bilayer. These conformational changes are critical for integrin activation and signaling across the plasma membrane. We thus propose a new model of integrin TM activation in which the recent NMR structure of the alpha(IIb)beta(3) TM/cytoplasmic complex represents an intermediate or transient state, and the electrostatic interaction in the cytoplasmic region is important for priming the initial alpha/beta association, but not absolutely necessary for the resting state.
authors: Department of Biological Sciences, Louisiana State University, 202 Life Sciences Building, Baton Rouge, Louisiana 70803, USA.
authors: Wei
authors: W
authors: Wang
authors: Bing-Hao
authors: BH
authors: Luo
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D016023:Integrins