PMID:9817758

Citation	Gregorio, CC, Trombitás, K, Centner, T, Kolmerer, B, Stier, G, Kunke, K, Suzuki, K, Obermayr, F, Herrmann, B, Granzier, H, Sorimachi, H and Labeit, S (1998) The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity. J. Cell Biol. 143:1013-27
Abstract	Titin is a giant elastic protein in vertebrate striated muscles with an unprecedented molecular mass of 3-4 megadaltons. Single molecules of titin extend from the Z-line to the M-line. Here, we define the molecular layout of titin within the Z-line; the most NH2-terminal 30 kD of titin is located at the periphery of the Z-line at the border of the adjacent sarcomere, whereas the subsequent 60 kD of titin spans the entire width of the Z-line. In vitro binding studies reveal that mammalian titins have at least four potential binding sites for alpha-actinin within their Z-line spanning region. Titin filaments may specify Z-line width and internal structure by varying the length of their NH2-terminal overlap and number of alpha-actinin binding sites that serve to cross-link the titin and thin filaments. Furthermore, we demonstrate that the NH2-terminal titin Ig repeats Z1 and Z2 in the periphery of the Z-line bind to a novel 19-kD protein, referred to as titin-cap. Using dominant-negative approaches in cardiac myocytes, both the titin Z1-Z2 domains and titin-cap are shown to be required for the structural integrity of sarcomeres, suggesting that their interaction is critical in titin filament-regulated sarcomeric assembly.
Links	PubMed PMC2132961
Keywords	Actinin/chemistry; Actinin/metabolism; Amino Acid Sequence; Animals; Cells, Cultured; Chick Embryo; Gene Expression/physiology; Membrane Proteins/chemistry; Membrane Proteins/genetics; Membrane Proteins/metabolism; Microscopy, Immunoelectron; Molecular Sequence Data; Muscle Fibers, Skeletal/cytology; Muscle Fibers, Skeletal/metabolism; Muscle Fibers, Skeletal/ultrastructure; Muscle Proteins/chemistry; Muscle Proteins/genetics; Muscle Proteins/metabolism; Muscle, Skeletal/chemistry; Muscle, Skeletal/cytology; Muscle, Skeletal/metabolism; Myocardium/chemistry; Myocardium/cytology; Myocardium/metabolism; Myofibrils/chemistry; Myofibrils/metabolism; Myofibrils/ultrastructure; Protein Kinases/chemistry; Protein Kinases/genetics; Protein Kinases/metabolism; Protein Structure, Tertiary; Sarcomeres/chemistry; Sarcomeres/metabolism; Sarcomeres/ultrastructure; Transcription, Genetic/physiology
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