Myosin 19, a novel class of myosin, is an actin-based high-duty molecular motor protein involved with the movement and positioning of mitochondria through binding to the MyMOMA tail region. It is important to biological systems as problems with mitochondrial localization can lead to a wide range of diseases in humans, most of them neuronal in nature. While the residue sequence of MYO19 is known, currently there is no known three-dimensional experimental structure. We seek to discover how binding ATP, ADP, and ADP+Pi to the nucleotide active site of this protein affects the structure-function of the wild-type and mutant MYO19 motor region. Theoretical structures of MYO19 have been computationally created by threading the MYO19 residue sequence on the Lorenz-Holmes Model of MYO2 and MYO5 PDB 1w7j using Phyre2, along with post-thread filling of missing sequences using Maestro 11. MYO19 mutants W140E and W140V have also been created through direct PDB editing to better understand the importance of tryptophan to nucleotide binding. Nucleotide induced conformational changes will be understood through molecular dynamics simulations (MD) and data analysis of the MYO19 potential energy surface using the AMBER 16 software suite. A deeper understanding of how nucleotide binding impacts the structure and function of MYO19 will lead to a greater knowledge of the causation of various mitochondrial diseases.

Computational investigation of myosin 19 structure-function

2019 Spring National Meeting

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