In collaboration with Simona Polo we identified a novel ubiquitin-binding domain in myosin VI and solved its structure by NMR spectroscopy. We named this domain myosin VI ubiquitin-binding domain (MyUb). We discovered myosin VI to prefer K63-linked chains, which are used for cell signaling rather than to signal for proteolysis. We solved the structure of MyUb complexed with K63-linked diubiquitin to find a unique recognition mode for this chain type. Moreover, we mapped the region required for myosin VI interaction with endocytosis and autophagy adaptors, which overlaps with the MyUb. Myosin VI is expressed in humans as short or long isoforms, such that MyUb is extended in the long isoforms to include an additional N-terminal helix. We found that certain cancers preferentially express short myosin VI isoforms and that myosin VI knockdown in these cells restricts cell migration. We are investigating the functional significance of this helical insert for interaction with various binding partners.
| Rao, Timsi; Gao, Rui; Takada, Saeko et al. (2016) Novel TDP2-ubiquitin interactions and their importance for the repair of topoisomerase II-mediated DNA damage. Nucleic Acids Res 44:10201-10215 |
| He, Fahu; Wollscheid, Hans-Peter; Nowicka, Urszula et al. (2016) Myosin VI Contains a Compact Structural Motif that Binds to Ubiquitin Chains. Cell Rep 14:2683-94 |
| Wollscheid, Hans-Peter; Biancospino, Matteo; He, Fahu et al. (2016) Diverse functions of myosin VI elucidated by an isoform-specific ?-helix domain. Nat Struct Mol Biol 23:300-308 |
