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Structure of a highly conserved domain of rock1 required for shroom-mediated regulation of cell morphology

Mohan, S and Das, D and Bauer, RJ and Heroux, A and Zalewski, JK and Heber, S and Dosunmu-Ogunbi, AM and Trakselis, MA and Hildebrand, JD and VanDemark, AP (2013) Structure of a highly conserved domain of rock1 required for shroom-mediated regulation of cell morphology. PLoS ONE, 8 (12).

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Abstract

Rho-associated coiled coil containing protein kinase (Rho-kinase or Rock) is a well-defined determinant of actin organization and dynamics in most animal cells characterized to date. One of the primary effectors of Rock is non-muscle myosin II. Activation of Rock results in increased contractility of myosin II and subsequent changes in actin architecture and cell morphology. The regulation of Rock is thought to occur via autoinhibition of the kinase domain via intramolecular interactions between the N-terminus and the C-terminus of the kinase. This autoinhibited state can be relieved via proteolytic cleavage, binding of lipids to a Pleckstrin Homology domain near the C-terminus, or binding of GTP-bound RhoA to the central coiled-coil region of Rock. Recent work has identified the Shroom family of proteins as an additional regulator of Rock either at the level of cellular distribution or catalytic activity or both. The Shroom-Rock complex is conserved in most animals and is essential for the formation of the neural tube, eye, and gut in vertebrates. To address the mechanism by which Shroom and Rock interact, we have solved the structure of the coiled-coil region of Rock that binds to Shroom proteins. Consistent with other observations, the Shroom binding domain is a parallel coiled-coil dimer. Using biochemical approaches, we have identified a large patch of residues that contribute to Shrm binding. Their orientation suggests that there may be two independent Shrm binding sites on opposing faces of the coiled-coil region of Rock. Finally, we show that the binding surface is essential for Rock colocalization with Shroom and for Shroom-mediated changes in cell morphology. © 2013 Mohan et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Mohan, S
Das, D
Bauer, RJ
Heroux, A
Zalewski, JKjkz3@pitt.eduJKZ3
Heber, S
Dosunmu-Ogunbi, AM
Trakselis, MA
Hildebrand, JDjeffh@pitt.eduJEFFH0000-0002-6173-7052
VanDemark, APandyv@pitt.eduANDYV0000-0003-3424-4831
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorFanning, Alan S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 9 December 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0081075
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
Date Deposited: 13 Jun 2014 19:00
Last Modified: 02 Feb 2019 16:58
URI: http://d-scholarship.pitt.edu/id/eprint/21850

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