Type of Document	Dissertation
Author	Ye, Feng
URN	etd-11142005-121816
Title	Integrin Alpha Iib Beta 3 Conformational Change Visualized in a Membrane Environment by Cryoelectron Tomography
Degree	Doctor of Philosophy
Department	Molecular Biophysics, Institute of
Advisory Committee	Advisor Name Title Michael S. Chapman Committee Chair Kenneth A. Taylor Committee Co-Chair Kenneth H. Roux Committee Member Thomas C. S. Keller III Committee Member Thomas M. Roberts Committee Member
Keywords	Cryoelectron Tomography Conformational Change Integrin
Date of Defense	2005-11-10
Availability	unrestricted
Abstract 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.
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