Nanoscale Approaches to Understanding Membrane Protein Function

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 DESCRIPTION (provided by applicant): Biological membranes are needed by all life forms. These lipid bilayers separate the inside and outside of the cell and, in higher organisms, provide the separation between internal compartments. As such, they are the site for processes of that provide recognition and communication and provide the home to a host of proteins that mediate signaling, catalysis and the generation and transduction of energy and the import and export of molecules. Despite this central role in life, membranes and membrane proteins have often been difficult to study using the normal tools of biochemistry and molecular biology. Membrane proteins display loss or altered activity when removed from their native lipid environment. Likewise, revealing the fundamental molecular recognition events involved in forming complex multi-component architectures at the membrane surface requires new methodologies. Nanodiscs, self-assembled nanoscale lipid bilayers solubilized by an amphipathic scaffold protein discovered in our laboratory, have served to enable new discoveries in these arenas. Under support from this award, we will further develop the Nanodisc system to provide novel biochemical and biophysical paths to the realization of the mechanisms involved in catalysis, signaling and molecular recognition. Complex macromolecular assemblies under investigation include those involved in blood coagulation, xenobiotic and hormone metabolism and cell transformation/migration.