Crystal structure of a coiled-coil domain from human ROCK I.

Publication Type:

Journal Article


PLoS One, Volume 6, Issue 3, p.e18080 (2011)


Amino Acid Sequence, Crystallography, X-Ray, Dimerization, Humans, Models, Molecular, Molecular Sequence Data, Protein Conformation, rho-Associated Kinases, Sequence Homology, Amino Acid, Tropomyosin


<p>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.</p>