title: The SH3 domain of UNC-89 (obscurin) interacts with paramyosin, a coiled-coil protein, in Caenorhabditis elegans muscle.
abstract: UNC-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.
authors.affiliation: Department of Pathology, Emory University, Atlanta, GA 30322.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Qadota
authors.affiliation: Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Mayans
authors.affiliation: Department of Pathology, Emory University, Atlanta, GA 30322.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Matsunaga
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA 30144.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: McMurry
authors.affiliation: Department of Pathology, Emory University, Atlanta, GA 30322.
authors.forename: Kristy J
authors.initials: KJ
authors.lastname: Wilson
authors.affiliation: Department of Pathology, Emory University, Atlanta, GA 30322.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Emory University, Atlanta, GA 30322.
authors.forename: Rachel
authors.initials: R
authors.lastname: Stanford
authors.affiliation: Department of Pathology, Emory University, Atlanta, GA 30322.
authors.forename: Kevin
authors.initials: K
authors.lastname: Deehan
authors.affiliation: Department of Pathology, Emory University, Atlanta, GA 30322.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Tinley
authors.affiliation: Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA 30144.
authors.forename: Verra M
authors.initials: VM
authors.lastname: Ngwa
authors.affiliation: Department of Pathology, Emory University, Atlanta, GA 30322 pathgb@emory.edu.
authors.forename: Guy M
authors.initials: GM
authors.lastname: Benian
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D012518:Sarcomeres / Q000378:metabolism; D013329:Structure-Activity Relationship; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D029742:Caenorhabditis elegans Proteins; D020662:Guanine Nucleotide Exchange Factors; D009124:Muscle Proteins; D010455:Peptides; D014335:Tropomyosin; C098932:Unc-89 protein, C elegans