800 MHZ NMR CRYOGENIC PROBE UPGRADE We propose to purchase a cryogenic triple resonance probe system (cold-probe with compressor and heat exchangers) for the existing Varian 800 MHz NMR system at the University of Michigan, which is dedicated to biomacromolecular studies serving the Biophysics, Chemistry, Biological Chemistry and Life-Sciences communities. This upgrade will serve two broad purposes: 1) it will extend the applicability of NMR in investigating the structure, dynamics and interactions of increasingly larger biological macromolecules and their complexes currently under study at our institution, and 2) it will enable us to more effectively meet the increasing demand for NMR time on the 800 MHz system by various investigators of our expanding biomolecular NMR user community. The 800 MHz instrument will be used for detailed solution NMR studies of large (up to 70 kDa) and marginally soluble (100 fM) biomacromolecules and their complexes. The projects encompass the elucidation of the structures, dynamics and interactions of allosteric Hsp70 chaperone proteins, of domains of the mitochondrial ATP-synthase, of domains of the HIV-1 RNA genome, of lectin-carbohydrate complexes, of micelle-solubilized membrane-peptides and -proteins, of bacterial RNase-P riboproteins, of bacterial 30S ribosome riboproteins and of complexes of cytochromes. The eight users of the instrument are broadly supported by multiple NIH R01 grants, and are either NMR experts (three), biochemists with NMR-trained post-docs (three), or biochemists who collaborate with the NMR experts (two).