NUCLEOTIDE INDUCED STRUCTURAL CHANGES IN MYOSINS

Scripps Research Institute, La Jolla CA

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Abstract

DESCRIPTION: (Adapted from abstract) The long term goals of this research are to visualize the conformational changes in the myosin head in both the attached and detached stages of the crossbridge cycle, and to place these observations within the context of mosin mechanochemistry. In the experiments described here, cryo-electron microscopy and image analysis will be used to answer the following fundamental questions: 1)Are the ADP-induced changes seen in smooth muscle myosin and brush border myosin I a charactistic of myosins in general? 2) Are there additional dramatic conformational changes associated with attached states earlier in the cycle? And 3) Is the conformation of the myosin head prior to actin attachment distinct from the ADP.Pi, ADP and rigor attached states? The data to be obtain is designed to establish general principles relating biochemical transitions, conformational changes and function in myosin motors, and pave the way for a more complete understanding of myosin mechanochemistry.