The shaker-1 mouse myosin VIIa deafness mutation results in a severely reduced rate of the ATP hydrolysis step.
Autor: | Xiong A; From the Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507., Haithcock J; From the Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507., Liu Y; From the Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507., Eusner L; From the Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507., McConnell M; From the Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507., White HD; From the Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507., Belknap B; From the Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507., Forgacs E; From the Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507 forgace@evms.edu. |
---|---|
Jazyk: | angličtina |
Zdroj: | The Journal of biological chemistry [J Biol Chem] 2018 Jan 19; Vol. 293 (3), pp. 819-829. Date of Electronic Publication: 2017 Nov 22. |
DOI: | 10.1074/jbc.M117.810119 |
Abstrakt: | Mutations in the MYO7A gene, encoding the motor protein myosin VIIa, can cause Usher 1B, a deafness/blindness syndrome in humans, and the shaker-1 phenotype, characterized by deafness, head tossing, and circling behavior, in mice. Myosin VIIa is responsible for tension bearing and the transduction mechanism in the stereocilia and for melanosome transport in the retina, in line with the phenotypic outcomes observed in mice. However, the effect of the shaker-1 mutation, a R502P amino acid substitution, on the motor function is unclear. To explore this question, we determined the kinetic properties and the effect on the filopodial tip localization of the recombinant mouse myosin VIIa-5IQ-SAH R502P (myoVIIa-sh1) construct. Interestingly, although residue 502 is localized to a region thought to be involved in interacting with actin, the kinetic parameters for actin binding changed only slightly for the mutant construct. However, the rate constant for ATP hydrolysis ( k (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.) |
Databáze: | MEDLINE |
Externí odkaz: |