title: Kinetic properties and small-molecule inhibition of human myosin-6.
abstract: Myosin-6 is an actin-based motor protein that moves its cargo towards the minus-end of actin filaments. Mutations in the gene encoding the myosin-6 heavy chain and changes in the cellular abundance of the protein have been linked to hypertrophic cardiomyopathy, neurodegenerative diseases, and cancer. Here, we present a detailed kinetic characterization of the human myosin-6 motor domain, describe the effect of 2,4,6-triiodophenol on the interaction of myosin-6 with F-actin and nucleotides, and show how addition of the drug reduces the number of myosin-6-dependent vesicle fusion events at the plasma membrane during constitutive secretion.
authors.affiliation: Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Heissler
authors.forename: Jayashankar
authors.initials: J
authors.lastname: Selvadurai
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Bond
authors.forename: Roman
authors.initials: R
authors.lastname: Fedorov
authors.forename: John
authors.initials: J
authors.lastname: Kendrick-Jones
authors.forename: Folma
authors.initials: F
authors.lastname: Buss
authors.forename: Dietmar J
authors.initials: DJ
authors.lastname: Manstein
mesh_terms: D000199:Actins / Q000378:metabolism; D051046:Amino-Acid N-Acetyltransferase; D000818:Animals; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D020409:Molecular Motor Proteins; D010636:Phenols; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C089785:myosin VI; C066859:2,4,6-triiodophenol; D051046:Amino-Acid N-Acetyltransferase; D018995:Myosin Heavy Chains