title: What makes tropomyosin an actin binding protein? A perspective.
abstract: Tropomyosin is a two-chained alpha-helical coiled coil that binds along the length of the actin filament and regulates its function. The paper addresses the question of how a "simple" coiled-coil sequence encodes the information for binding and regulating the actin filament, its universal target. Determination of the tropomyosin sequence confirmed Crick's predicted heptapeptide repeat of hydrophobic interface residues and revealed additional features that have been shown to be important for its function: a 7-fold periodicity predicted to correspond to actin binding sites and interruptions of the canonical interface with destabilizing residues, such as Ala. Evidence from published work is summarized, leading to the proposal of a paradigm that binding of tropomyosin to the actin filament requires local instability as well as regions of flexibility. The flexibility derives from bends and local unfolding at regions with a destabilized coiled-coil interface, as well as from the dynamic end-to-end complex. The features are required for tropomyosin to assume the form of the helical actin filament, and to bind to actin monomers along its length. The requirement of instability/flexibility for binding may be generalized to the binding of other coiled coils to their targets.
authors.affiliation: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA. hitchcoc@umdnj.edu
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hitchcock-DeGregori
authors.forename: Abhishek
authors.initials: A
authors.lastname: Singh
mesh_terms: D000199:Actins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014335:Tropomyosin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D021122:Protein Subunits; D014335:Tropomyosin