CHEMO-MECHANICAL TRANSDUCTION--HEART/SKELETAL MUSCLE

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It is proposed to examine experimentally critical points in the PI's theory of chemo-mechanical energy transduction in heart/skeletal muscle: "Each ligated ATP derivative in the procession of "intermediates" at the ATPase site of myosin S-l transmits characteristic signals to the remote actin-binding site of the same S-l, there directing geometrical relations between S- l and actin; thus the ATPase cycle compels the relational (potential work) cycle. The signals are distinctive patterns of tension and displacement in the S-l structure intervening between sites. This project aims to locate sites and transmitter structures, and generally to understand the operation of this micro-machine. Several not yet widely used methods in muscle are proposed: FRET-estimated interpoint distance lattices, "designer" anti-peptides targeted to site, novel metal detections on S-l and actin, resolution of actomyosin affinities into coulombic and hydrophobic components, etc. Success of the project would result in true molecular level understanding of energy utilization in heart/skeletal muscle. Proposed work is focussed outgrowth of applicants' previous work under NHLBI HL-16683.