SOLUTE TRANSPORT TAXIS AND SENSORY PATHWAY RECEPTORS

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DESCRIPTION: The structure and function of a number of binding proteins (or receptors) are to be determined. Whereas, X-ray crystallography is the primary experimental approach which will be used, biochemical, recombinant DNA and computational techniques will also be employed. These proteins - with specificity for a variety of carbohydrates, oxyacids (sulfate and phosphate), amino acids, dipeptides and oligopeptides - serve as initial high affinity receptors of ATP-driven transport systems or permeases in bacteria. This group of permeases is a member of a superfamily of ATP binding transporters found not only in prokaryotes but also in eukaryotes (e.g. the mammalian P-glycoprotein multi-drug resistance gene product and the cystic fibrosis transmembrane conductance regulator). Three of the binding proteins also serve as primary chemoreceptors in the simple behavioral response of chemotaxis. It is proposed to refine the structures of the liganded forms of selected binding proteins (e.g. those with specificity of phosphate, sulfate, arabinose, maltose-binding protein, leucine/isoleucine/valine) close to 1 A resolution using SHELXL. The wide variety of solutes or nutrients recognized by the family of receptors and the wide spectrum in the degree of specificity from the most stringent (e.g. phosphate) to the most loose (oligopeptides) is an opportunity for detailed study of molecular recognition. Of particular interest are the relative contributions of electrostatic and hydrophobic interactions. Computational techniques are to be explored to evaluate their predictive value as to the relative contribution of these interactions to specific molecular recognition paradigms in the receptor family (phosphate vs. sulfate, mono- vs. oligosaccharides, peptides vs. amino acids, etc.). The receptors offer an excellent opportunity to delve into structural features of a family of proteins which range in size from about 25 to 60 kDa and share little sequence homology, yet presumably fold into a similar overall three-dimensional structure.