title: Crystal structure of the C-terminal half of tropomodulin and structural basis of actin filament pointed-end capping.
abstract: Tropomodulin is the unique pointed-end capping protein of the actin-tropomyosin filament. By blocking elongation and depolymerization, tropomodulin regulates the architecture and the dynamics of the filament. Here we report the crystal structure at 1.45-A resolution of the C-terminal half of tropomodulin (C20), the actin-binding moiety of tropomodulin. C20 is a leucine-rich repeat domain, and this is the first actin-associated protein with a leucine-rich repeat. Binding assays suggested that C20 also interacts with the N-terminal fragment, M1-M2-M3, of nebulin. Based on the crystal structure, we propose a model for C20 docking to the actin subunit at the pointed end. Although speculative, the model is consistent with the idea that a tropomodulin molecule competes with an actin subunit for a pointed end. The model also suggests that interactions with tropomyosin, actin, and nebulin are all possible sources of influences on the dynamic properties of pointed-end capping by tropomodulin.
authors.affiliation: Laboratory for Structural Biochemistry, RIKEN Harima Institute at SPring-8, Mikazuki, Sayo, Hyogo, Japan 679-5148.
authors.forename: Inna
authors.initials: I
authors.lastname: Krieger
authors.forename: Alla
authors.initials: A
authors.lastname: Kostyukova
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yamashita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nitanai
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maéda
mesh_terms: D000199:Actins / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry*; D002645:Chickens; D018360:Crystallography, X-Ray; D008840:Microfilament Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D051348:Tropomodulin
chemical_list: D000199:Actins; D002352:Carrier Proteins; D008840:Microfilament Proteins; D051348:Tropomodulin