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A novel ubiquitin-binding domain in myosin VI with specificity for Lys63 linked ubiquitin chains

Wednesday, September 24, 2014 — Poster Session IV

10:00 a.m. –12:00 p.m.

FAES Academic Center



* FARE Award Winner


  • F. He
  • H. Wollscheild
  • A. Ehlinger
  • S. Polo
  • K.J. Walters


Myosins are motor proteins that use energy derived from ATP hydrolysis to generate force and move along actin filaments. Humans have ~40 known or predicted myosins that participate in diverse activities, including intracellular trafficking, cell division and motility, actin cytoskeletal organization, and cell signaling. Myosin malfunction has been implicated in hypertrophic cardiomyopathy, Usher syndrome, deafness, Griscelli syndrome, and cancer. Myosin VI moves along actin filaments in the opposite direction compared to all other myosins and has recently been implicated in endocytosis and autophagy. We report that myosin VI joins the growing family of ubiquitin receptors with a unique ubiquitin-binding element (MyUb). MyUb adopts a compact 42-amino acid helix-turn-helix-like motif with an N-terminal extension that is critical for structure integrity and MyUb intact structure is required for myosin VI function. We have found MyUb to prefer K63-linked ubiquitin chains and solved the MyUb:K63 diubiquitin structure, which places MyUb wedged between neighboring ubiquitins with unique interactions to each. Myosin VI contains an MIU element N-terminal to MyUb and we demonstrate that this region also binds ubiquitin. In the MIU-MyUb fragment, the two ubiquitin-binding domains bind simultaneously to ubiquitin components of K63-linked diubiquitin. Altogether, these finding suggest that myosin VI function is ubiquitin-dependent.

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