Kinetic properties and small-molecule inhibition of human myosin-6

FEBS Lett. 2012 Sep 21;586(19):3208-14. doi: 10.1016/j.febslet.2012.07.014. Epub 2012 Jul 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Amino-Acid N-Acetyltransferase
  • Animals
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Models, Biological
  • Models, Molecular
  • Molecular Motor Proteins / antagonists & inhibitors
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / genetics
  • Molecular Motor Proteins / metabolism
  • Mutagenesis, Site-Directed
  • Myosin Heavy Chains / antagonists & inhibitors*
  • Myosin Heavy Chains / chemistry
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism*
  • Phenols / pharmacology
  • Protein Interaction Domains and Motifs
  • RNA, Small Interfering / genetics
  • Rabbits
  • Recombinant Fusion Proteins / antagonists & inhibitors
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • Actins
  • Molecular Motor Proteins
  • Phenols
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • myosin VI
  • 2,4,6-triiodophenol
  • Amino-Acid N-Acetyltransferase
  • Myosin Heavy Chains