Integrin signaling is critical for many biological functions including cell survival, cell migration, development, immunity and wound healing. Integrins perform their function through a structural change that is propagated from the cytoplasm to the ligand binding domain in inside-out signaling and from the ligand binding domain to the cytoplasm during outside-in signaling events. However, the structural basis for the signal transduction in a native-like lipid bilayer environment is poorly understood. We investigated the inactive and active conformations of integrin alpha IIb beta 3 in a membrane environment to understand the structural basis of integrin signaling. We used reconstituted small unilamellar vesicles to mimic the native membrane environment and used cryo-electron tomography of ice embedded specimens and 3-D averaging to obtain the structures. Our results showed that, in this membrane environment, both active and inactive integrins are in an upright conformation. They differ in the separation of the leg regions of the alpha and beta chains. Inactive integrins have the legs together, similar to the 3-D structure of detergent solubilized alpha IIb beta 3 observed in ice but with a more upright orientation with respect to the membrane. The active integrins have the legs separated by about 5.6 nm at the membrane surface. These results support a model in which integrin signaling is achieved by the relative movement of the leg regions of the two subunits. / A Dissertation submitted to the Institute of Molecular Biophysics in partial
fulfillment of the requirements for the degree of Doctor of Philosophy. / Degree Awarded: Fall Semester, 2005. / Date of Defense: November 10, 2005. / Cryoelectron Tomography, Conformational Change, Integrin / Includes bibliographical references. / Kenneth A. Taylor, Professor Directing Dissertation; Michael S. Chapman, Outside Committee Member; Thomas M. Roberts, Committee Member; Thomas C. S. Keller III, Committee Member; Kenneth H. Roux, Committee Member.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_168563 |
| Contributors | Ye, Feng (authoraut), Taylor, Kenneth A. (professor directing dissertation), Chapman, Michael S. (outside committee member), Roberts, Thomas M. (committee member), III, Thomas C. S. Keller (committee member), Roux, Kenneth H. (committee member), Program in Molecular Biophysics (degree granting department), Florida State University (degree granting institution) |
| Publisher | Florida State University |
| Source Sets | Florida State University |
| Language | English, English |
| Detected Language | English |
| Type | Text, text |
| Format | 1 online resource, computer, application/pdf |
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