600 MHZ NUCLEAR MAGNETIC RESONANCE SPECTROMETER

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We request funds to purchase a state-of-the-art 600 MHz nuclear magnetic resonance spectrometer to support the research of a group of NIH- sponsored major users (Gierasch, Decatur, Maroney, Thompson, Weis, Zimmermann), whose research will require 85% of the instrument time. The remaining time of the instrument will be allotted to minor users (Gross, Hong, Martin, Rotello, Krejsa) and to maintenance and implementation of new experiments by the NMR Facility Manager and Associate Manager. The major research projects that will be facilitated by the availability of the requested instrumentation include: determination of the structure of the peptide-binding domains of the molecular chaperones DnaK and BiP; determination of the bound conformation of signal sequences upon interaction with their receptors; determination of the structure of an SRP-binding RNA fragment alone and in complex with a polypeptide; studies of the mechanism of folding of the predominantly beta-sheet protein, cellular retinoic acid binding protein; structural analysis of myoglobin mutants as models for guanylate cyclase; conformational studies of model helical peptides; determination of the structure and dynamics of membrane proteins, including E. coli chemotactic receptors and colicin A; studies of domains of the E. coli chemotactic receptor that are involved in adaptation; and determination of the structures or ribosomal proteins and the RNAs to which they bind. Minor projects that will benefit from the availability of this instrumentation include: studies of bound conformations of EGF receptor fragments upon interactions with actin; structural characterization of difficult sequences for peptide synthesis; structural studies of domain of T7 RNA polymerase; structural studies of models for flavin cofactors and their environmental perturbations; and correlation of crosslinker structure with physical and chemical properties of nylons.