MOLECULAR STRUCTURE OF BIOLOGICAL MOLECULES

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The biological importance of membrane proteins has been underscored by the discovery that at least 25% of all genes in genomic databases have putative transmembrane helices. Yet, there are few structure for membrane proteins, largely because it is hard to create a soluble, stable state for study. We propose to explore alternative methods for structure determination for membrane proteins. We have succeeded in a re-design of phospholamban, a pentameric membrane protein, leading to a stable, pentameric, water-soluble structure that gives long-range NOE signals in NMR. We will use this molecule as a lead compound to explore the principles of stability and aqueous solubility for re-engineering membrane proteins. We will examine the structure of selected signs by NMR and attempt and attempt crystallization. As an alternative to the use of re-design, we will examine the properties of new class of surfactant, polymeric amphiphiles, which has considerable advantages over conventional surfactants, and may provide a new direction for NMR and/or crystallography. We will use solution scattering to measure the thickness of membranes and bilayers of lipids from them. We will continue our use of solution scattering to examine issues of oligomerization and folding of soluble and membrane proteins.