title: Crystal structure of a coiled-coil domain from human ROCK I.
abstract: The small GTPase Rho and one of its targets, Rho-associated kinase (ROCK), participate in a variety of actin-based cellular processes including smooth muscle contraction, cell migration, and stress fiber formation. The ROCK protein consists of an N-terminal kinase domain, a central coiled-coil domain containing a Rho binding site, and a C-terminal pleckstrin homology domain. Here we present the crystal structure of a large section of the central coiled-coil domain of human ROCK I (amino acids 535-700). The structure forms a parallel α-helical coiled-coil dimer that is structurally similar to tropomyosin, an actin filament binding protein. There is an unusual discontinuity in the coiled-coil; three charged residues (E613, R617 and D620) are positioned at what is normally the hydrophobic core of coiled-coil packing. We speculate that this conserved irregularity could function as a hinge that allows ROCK to adopt its autoinhibited conformation.
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Daqi
authors: D
authors: Tu
authors: Yiqun
authors: Y
authors: Li
authors: Hyun Kyu
authors: HK
authors: Song
authors: Angela V
authors: AV
authors: Toms
authors: Christopher J
authors: CJ
authors: Gould
authors: Scott B
authors: SB
authors: Ficarro
authors: Jarrod A
authors: JA
authors: Marto
authors: Bruce L
authors: BL
authors: Goode
authors: Michael J
authors: MJ
authors: Eck
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014335:Tropomyosin / Q000737:chemistry; D054460:rho-Associated Kinases / Q000737:chemistry*
chemical_list: D014335:Tropomyosin; D054460:rho-Associated Kinases