Mechanism of regulation of Acanthamoeba myosin-IC by heavy-chain phosphorylation

E. Michael Ostap, Tianming Lin, Steven S. Rosenfeld, Nanyun Tang

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


The ATPase activity of myosin-Is from lower eukaryotes is activated by phosphorylation by the p21-activated kinase family at the TEDS site on an actin-binding surface-loop. This actin-binding loop is the site of a cardiac myosin-II mutation responsible for some forms of familial hypertrophic cardiomyopathy. To determine the mechanism of myosin-I regulation by heavy-chain phosphorylation (HCP) and to better understand the importance of this loop in the function of all myosin isoforms, we performed a kinetic investigation of the regulatory mechanism of the Acanthamoeba myosin-IC motor domain (MICIQ). Phosphorylated and dephosphorylated MICIQ show actin-activated ATPase activity; however, HCP increases the ATPase activity > 20-fold. HCP does not greatly affect the rate of phosphate release from MIC in the absence of actin, as determined by single turnover experiments. Additionally, HCP does not significantly affect the affinity of myosin for actin in the absence or presence of ATP, the rate of ATP-induced dissociation of actoMICIQ, the affinity of ADP, or the rate of ADP release. Sequential-mix single-turnover experiments show that HCP regulates the rate of phosphate release from actin-bound MICIQ. We propose that the TEDS-containing actin-binding loop plays a direct role in regulating phosphate release and the force-generating (A-to-R) transition of myosin-IC.

Original languageEnglish (US)
Pages (from-to)12450-12456
Number of pages7
Issue number41
StatePublished - Oct 15 2002

ASJC Scopus subject areas

  • Biochemistry


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