title: Evidence for the oligomeric state of 'elastic' titin in muscle sarcomeres.
abstract: The giant protein titin has important roles in muscle sarcomere integrity, elasticity and contractile activity. The key role in elasticity was highlighted in recent years by single-molecule mechanical studies, which showed a direct relationship between the non-uniform structure of titin and the hierarchical mechanism of its force-extension behavior. Further advances in understanding mechanisms controlling sarcomere structure and elasticity require detailed knowledge of titin arrangement and interactions in situ. Here we present data on the structure and self-interactive properties of an approximately 290 kDa ( approximately 100 nm long) tryptic fragment from the I-band part of titin that is extensible in situ. The fragment includes the conserved 'distal' tandem Ig segment of the molecule and forms side-by-side oligomers with distinctive 4 nm cross-striations. Comparisons between these oligomers and the end filaments seen at the tips of native thick filaments indicate identical structure. This shows that end-filaments are formed by the elastic parts of six titin molecules connecting each end of the thick filament to the Z-line. Self-association of elastic titin into stiff end-filaments adds a further hierarchical level in the mechanism of titin extensibility in muscle cells. Self-association of this part of titin may be required to prevent interference of the individual flexible molecules with myosin cross-bridges interacting with actin.
authors.affiliation: Institute for Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Houmeida
authors.forename: Andy
authors.initials: A
authors.lastname: Baron
authors.forename: Jeff
authors.initials: J
authors.lastname: Keen
authors.forename: G Nasir
authors.initials: GN
authors.lastname: Khan
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Knight
authors.forename: Walter F
authors.initials: WF
authors.lastname: Stafford
authors.forename: Kavitha
authors.initials: K
authors.lastname: Thirumurugan
authors.forename: Beatrix
authors.initials: B
authors.lastname: Thompson
authors.forename: Larissa
authors.initials: L
authors.lastname: Tskhovrebova
authors.forename: John
authors.initials: J
authors.lastname: Trinick
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D064211:Connectin; D004548:Elasticity; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009124:Muscle Proteins / Q000737:chemistry* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000737:chemistry / Q000648:ultrastructure; D011494:Protein Kinases / Q000737:chemistry* / Q000648:ultrastructure; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D011817:Rabbits; D012518:Sarcomeres / Q000737:chemistry*; D020539:Sequence Analysis, Protein; D014461:Ultracentrifugation
chemical_list: D064211:Connectin; D009124:Muscle Proteins; D010446:Peptide Fragments; D011494:Protein Kinases