title: Structure of the mid-region of tropomyosin: bending and binding sites for actin.
abstract: Tropomyosin is a two-chain alpha-helical coiled coil whose periodic interactions with the F-actin helix are critical for thin filament stabilization and the regulation of muscle contraction. Here we deduce the mechanical and chemical basis of these interactions from the 2.3-A-resolution crystal structure of the middle three of tropomyosin's seven periods. Geometrically specific bends of the coiled coil, produced by clusters of core alanines, and variable bends about gaps in the core, produced by isolated alanines, occur along the molecule. The crystal packing is notable in signifying that the functionally important fifth period includes an especially favorable protein-binding site, comprising an unusual apolar patch on the surface together with surrounding charged residues. Based on these and other results, we have constructed a specific model of the thin filament, with the N-terminal halves of each period (i.e., the so-called "alpha zones") of tropomyosin axially aligned with subdomain 3 of each monomer in F-actin.
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454-9110, USA.
authors.forename: Jerry H
authors.initials: JH
authors.lastname: Brown
authors.forename: Zhaocai
authors.initials: Z
authors.lastname: Zhou
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Reshetnikova
authors.forename: Howard
authors.initials: H
authors.lastname: Robinson
authors.forename: Rama D
authors.initials: RD
authors.lastname: Yammani
authors.forename: Larry S
authors.initials: LS
authors.lastname: Tobacman
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cohen
mesh_terms: D051339:Actin Depolymerizing Factors / Q000737:chemistry; D000199:Actins / Q000737:chemistry*; D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D013696:Temperature; D051348:Tropomodulin / Q000737:chemistry; D014335:Tropomyosin / Q000737:chemistry*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D051348:Tropomodulin; D014335:Tropomyosin; D000409:Alanine; D002118:Calcium