crystal structure of a coiled-coil domain from human rock i晶体从人类摇滚我卷曲螺旋结构域.pdfVIP

Crystal Structure of a Coiled-Coil Domain from Human ROCK I Daqi Tu1,2, Yiqun Li2, Hyun Kyu Song3, Angela V. Toms 1,2, Christopher J. Gould4, Scott B. Ficarro 1,2, Jarrod A. Marto 1,2, Bruce L. Goode4, Michael J. Eck 1,2* 1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America, 3 School of Life Sciences and Biotechnology, Korea University, Seoul, Korea, 4 Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts, United States of America 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 a-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. Citation: Tu D, Li Y, Song HK, Toms AV, Gould CJ, et al. (2011) Crystal Structure of a Coiled-Coil Domain from Human ROCK I. PLoS ONE 6(3): e18080. doi:10.1371/ jo