The SH3 Domain of UNC-89 (obscurin) Interacts with Paramyosin, a Coiled-coil Protein, in Caenorhabditis Elegans MuscleMolecular Biology of the Cell
AbstractUNC-89 is a giant polypeptide located at the sarcomeric M-line of Caenorhabditis elegans muscle. The human homologue is obscurin. To understand how UNC-89 is localized and functions, we have been identifying its binding partners. Screening a yeast two-hybrid library revealed that UNC-89 interacts with paramyosin. Paramyosin is an invertebrate-specific coiled-coil dimer protein that is homologous to the rod portion of myosin heavy chains and resides in thick filament cores. Minimally, this interaction requires UNC-89’s SH3 domain and residues 294–376 of paramyosin and has a KD of ∼1.1 μM. In unc-89 loss-of-function mutants that lack the SH3 domain, paramyosin is found in accumulations. When the SH3 domain is overexpressed, paramyosin is mislocalized. SH3 domains usually interact with a proline-rich consensus sequence, but the region of paramyosin that interacts with UNC-89’s SH3 is α-helical and lacks prolines. Homology modeling of UNC-89’s SH3 suggests structural features that might be responsible for this interaction. The SH3-binding region of paramyosin contains a “skip residue,” which is likely to locally unwind the coiled-coil and perhaps contributes to the binding specificity.
Digital Object Identifier (DOI)10.1091/mbc.E15-09-0675
Citation InformationHiroshi Qadota, Jonathan McMurry, Verra M. Ngwa and Et al.. "The SH3 Domain of UNC-89 (obscurin) Interacts with Paramyosin, a Coiled-coil Protein, in Caenorhabditis Elegans Muscle" Molecular Biology of the Cell Vol. 27 Iss. 10 (2016) ISSN: 1939-4586
Available at: http://works.bepress.com/jonathan_mcmurry/61/