STRUCTURAL MECHANISM OF INTEGRIN ACTIVATIN INDUCED BY TALIN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Integrins are heterodimeric transmembrane molecules that mediate cell adhesion to extracellular matrix or to another cell. Structural studies indicate that integrin undergo large conformational changes in response to stimuli from outside or inside the cell. Talins play very important role in the inside-out processes. It has been suggested that talins compete with the integrin alpha subunit tails for beta cytoplasmic tails to activate integrins. The interactions of talin with cell membrane may introduce conformational changes on talin and facilitate the activation process. Here we will use molecular dynamics simulations to test the current talin induced integrin activation model and illustrate the structural basis.