Myosin VI deafness mutation prevents the initiation of processive runs on actin - Institut Curie Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2015

Myosin VI deafness mutation prevents the initiation of processive runs on actin

Olena Pylypenko
Lin Song
  • Fonction : Auteur
Ai Shima
  • Fonction : Auteur
Zhaohui Yang
  • Fonction : Auteur
Anne Houdusse
H Lee Sweeney
  • Fonction : Auteur

Résumé

Mutations in the reverse-direction myosin, myosin VI, are associated with deafness in humans and mice. A myosin VI deafness mutation, D179Y, which is in the transducer of the motor, uncoupled the release of the ATP hydrolysis product, inorganic phosphate (P i), from dependency on actin binding and destroyed the ability of single dimeric molecules to move processively on actin filaments. We observed that processive movement is rescued if ATP is added to the mutant dimer following binding of both heads to actin in the absence of ATP, demonstrating that the mutation selectively destroys the initiation of processive runs at physiological ATP levels. A drug (omecamtiv) that accelerates the actin-activated activity of cardiac myosin was able to rescue processivity of the D179Y mutant dimers at physiological ATP concentrations by slowing the actin-independent release of P i. Thus, it may be possible to create myosin VI-specific drugs that rescue the function of deafness-causing mutations. unconventional myosin | deafness | motility | processive movement | omecamtiv Data deposition: Crystallography, atomic coordinates, and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 4DBP, 4DBQ, and 4DBR).
Fichier principal
Vignette du fichier
E1201.full.pdf (1.49 Mo) Télécharger le fichier
Origine : Accord explicite pour ce dépôt

Dates et versions

hal-03059375 , version 1 (14-12-2020)

Identifiants

Citer

Olena Pylypenko, Lin Song, Ai Shima, Zhaohui Yang, Anne Houdusse, et al.. Myosin VI deafness mutation prevents the initiation of processive runs on actin. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112, pp.E1201 - E1209. ⟨10.1073/pnas.1420989112⟩. ⟨hal-03059375⟩
40 Consultations
27 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More