title: Identification of alpha-syntrophin binding to syntrophin triplet, dystrophin, and utrophin.
abstract: Syntrophin represents three cytoplasmic components of the dystrophin-glycoprotein complex that links the cytoskeleton to the extracellular matrix in skeletal muscle. alpha-Syntrophin has now been translated in vitro and shown to associate directly with all three components of the syntrophin triplet and with dystrophin. The in vitro translated 71-kDa non-muscle dystrophin isoform, containing the cystein-rich/C-terminal domain, can also interact with the syntrophin triplet. The syntrophin binding motif in dystrophin was localized to exons 73 and 74 including amino acids 3447-3481 by comparing the interactions of alpha-syntrophin and seven overlapping human dystrophin fusion proteins. More than one syntrophin interaction site in this binding motif was suggested. alpha-Syntrophin also interacts directly with a C-terminal utrophin fusion protein. alpha-Syntrophin is localized to the muscle sarcolemma as well as to the neuromuscular junction in control mouse muscle. However, similar to utrophin, alpha-syntrophin is only present at the neuromuscular junction in mdx mouse muscle in which dystrophin is absent. Our data suggest that alpha-syntrophin binds all syntrophin isoforms, and syntrophin directly interacts with dystrophin through more than one binding site in dystrophin exons 73 and 74 including amino acids 3447-3481.
authors.affiliation: Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.forename: D
authors.initials: D
authors.lastname: Jung
authors.forename: J A
authors.initials: JA
authors.lastname: Rafael
authors.forename: J S
authors.initials: JS
authors.lastname: Chamberlain
authors.forename: K P
authors.initials: KP
authors.lastname: Campbell
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D017931:DNA Primers; D016189:Dystrophin / Q000378:metabolism*; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D005091:Exons; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D058619:Maltose-Binding Proteins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D049411:Utrophin
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D016189:Dystrophin; D029968:Escherichia coli Proteins; D058619:Maltose-Binding Proteins; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011993:Recombinant Fusion Proteins; C483600:Utrn protein, mouse; D049411:Utrophin; C461599:maltose transport system, E coli; C091825:syntrophin alpha1; D005982:Glutathione Transferase