Continued studies are proposed to elucidate the mechanisms by which targeting sequences (including signal sequences and organellar localization sequences) facilitate correct localization of nascent polypeptide products. The emphasis of this proposal is the development of sequence/function correlations. We will use chemically synthesized targeting sequences and a number of biophysical methods to analyze them: circular dichroism (CD), nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and surface tensiometry; peptide/lipid interactions will be probed in micelle, vesicle and multilayer systems. Our working hypothesis, supported by our results on signal sequences, is that there are intrinsic properties of targeting sequences that confer upon them the ability to interact productibly with cellular components and to mediate the process of protein localization. These properties will be assessed by biophysical and biochemical study of the isolated targeting sequences, of targeting sequences linked to portions of their cognate protein products, and of targeting sequences in combination with other cellular components (e.g., membranes, SRP, export factors). The importance of the context in which a targeting sequence is presented will also be investigated. Through collaborative interactions, our results will be integrated with genetic and cellular biological characterization of the targeting sequences.
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