EFFECTORS OF ORGANIZATION OF TRANSMEMBRANE PROTEINS

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The conformation of constitutive membrane proteins is poorly understood and the effect of membrane lipids on these proteins, or on those that must traverse membranes in intracellular traffic, is also in need of clarification. In this project, two proteins, the acetylcholine receptor (AcChR) and a precursor to a mitochondrial matrix protein, aspartate aminotransferase (pmAAT), are used as models to gain greater understanding of the above problems. In the first case, particular attention is paid to the development of quantitative techniques to assign specific lysyl residues in the sequence of all the constitutive subunits to the cytoplasmic side of the membrane, which is a region largely unexplored in transmembranous proteins. Characterization of contact points between AcChR and specific neurotoxins and selected antibodies against synaptic (exterior) side will also be carried out, as well as the effect of such protein-protein interactions in the exposure of the (distant) cytoplasmic side lysyl residues. iN the second protein system, the availability of a precursor as an isolated, soluble, stable protein provides the first opportunity to observe precursor-membrane interactions under controlled conditions. Thus, in pmAAT, the role of the presequence consequences of such on precursor structure, will be assessed by antibodies and a variety of biophysical tools.