Expression Studies of Other Unconventional Myosins

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We have begun to analyze the structure and stepping pattern of myosin-6, a processive myosin which moves in the opposite direction on actin compared to other myosins. EM studies show that the angle between the two heads is more variable than in most myosins and that when bound to actin, the motors can be spaced at 13 actins (preferred) or 11 or 15 actin monomers apart. Optical trapping and EM studies demonstrate that the molecule can sometimes take an "inchworm" like step where the two heads occupy closely spaced binding sites. Myosin 7a is present in the stereocilia of the inner ear and in retinal cells. Mutations of this myosin have been associated with deafness and blindness. We have expressed full length mammalian myosin 7a and find that it is autoinhibited, similiar to what we found with its Drosophila homolog. MyoRip, a myosin 7a binding partner, relieves this autoinhibition and allows for processive movements. We are also exploring whether known myosin 7a interacting partners present in the inner ear interact with the myosin and relieve autoinhibition. In collaboration with John Hammer we have begun to study myosin 19 a mitochondrial associated myosin to complement ongoing cell biological studies.