title: Titin and the sarcomere symmetry paradox.
abstract: Titin is thought to play a major role in myofibril assembly, elasticity and stability. A single molecule spans half the sarcomere and makes interactions with both a thick filament and the Z-line. In the unit cell structure of each half sarcomere there is one thick filament with 3-fold symmetry and two thin filaments with approximately 2-fold symmetry. The minimum number of titin molecules that could satisfy both these symmetries is 12. We determined the actual number of titin molecules in a unit cell from scanning transmission electron microscopy mass measurements of end-filaments. One of these emerges from each tip of the thick filament and is thought to be the in-register aggregate of the titin molecules associated with the filament. The mass per unit length of the end-filament (17.1 kDa/nm) is consistent with six titin molecules not 12. Thus the number of titin molecules present is insufficient to satisfy both symmetries. We suggest a novel solution to this paradox in which four of the six titin molecules interact with the two thin filaments in the unit cell, while the remaining two interact with the two thin filaments that enter the unit cell from the adjacent sarcomere. This arrangement would augment mechanical stability in the sarcomere.
authors.affiliation: School of Biomedical Sciences, Leeds University, Leeds, LS2 9JT, UK.
authors.forename: A D
authors.initials: AD
authors.lastname: Liversage
authors.forename: D
authors.initials: D
authors.lastname: Holmes
authors.forename: P J
authors.initials: PJ
authors.lastname: Knight
authors.forename: L
authors.initials: L
authors.lastname: Tskhovrebova
authors.forename: J
authors.initials: J
authors.lastname: Trinick
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D000818:Animals; D002645:Chickens; D064211:Connectin; D051379:Mice; D017348:Microscopy, Electron, Scanning Transmission; D008958:Models, Molecular; D008970:Molecular Weight; D009124:Muscle Proteins / Q000032:analysis* / Q000378:metabolism / Q000648:ultrastructure*; D011494:Protein Kinases / Q000032:analysis* / Q000378:metabolism / Q000648:ultrastructure*; D011817:Rabbits; D011894:Rana pipiens; D051381:Rats; D012518:Sarcomeres / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D013552:Swine
chemical_list: D064211:Connectin; D009124:Muscle Proteins; D011494:Protein Kinases