2V55

Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structure

Summary for 2V55

• Entry DOI: 10.2210/pdb2v55/pdb
• Related: 1M7B 1S1C 2ESM 2ETK 2ETO 2ETR
• Descriptor: RHO-ASSOCIATED PROTEIN KINASE 1, RHO-RELATED GTP-BINDING PROTEIN RHOE, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (6 entities in total)
• Functional Keywords: serine/threonine-protein kinase, rhoe, zinc, kinase, rock-i, membrane, apoptosis, cytoplasm, g-proteins, methylation, zinc-finger, nucleotide-binding, phorbol-ester binding, atp-binding, prenylation, transferase, lipoprotein, multi-site phosphorylation, coiled coil, gtp-binding, polymorphism, stress fibres, metal-binding, phosphoprotein, golgi apparatus
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm: Q13464; Golgi apparatus membrane; Peripheral membrane protein: P61587
• Total number of polymer chains: 4
• Total formula weight: 141147.40

Authors

Komander, D.,Garg, R.,Wan, P.T.C.,Ridley, A.J.,Barford, D. (deposition date: 2008-10-01, release date: 2008-11-04, Last modification date: 2023-12-13)

Primary citation

Komander, D.,Garg, R.,Wan, P.T.C.,Ridley, A.J.,Barford, D.
Mechanism of Multi-Site Phosphorylation from a Rock-I:Rhoe Complex Structure.
Embo J., 27:3175-, 2008

PubMed Abstract: The ROCK-I serine/threonine protein kinase mediates the effects of RhoA to promote the formation of actin stress fibres and integrin-based focal adhesions. ROCK-I phosphorylates the unconventional G-protein RhoE on multiple N- and C-terminal sites. These phosphorylation events stabilise RhoE, which functions to antagonise RhoA-induced stress fibre assembly. Here, we provide a molecular explanation for multi-site phosphorylation of RhoE from the crystal structure of RhoE in complex with the ROCK-I kinase domain. RhoE interacts with the C-lobe alphaG helix of ROCK-I by means of a novel binding site remote from its effector region, positioning its N and C termini proximal to the ROCK-I catalytic site. Disruption of the ROCK-I:RhoE interface abolishes RhoE phosphorylation, but has no effect on the ability of RhoE to disassemble stress fibres. In contrast, mutation of the RhoE effector region attenuates RhoE-mediated disruption of the actin cytoskeleton, indicating that RhoE exerts its inhibitory effects on ROCK-I through protein(s) binding to its effector region. We propose that ROCK-I phosphorylation of RhoE forms part of a feedback loop to regulate RhoA signalling.

PubMed: 18946488
DOI: 10.1038/EMBOJ.2008.226

Experimental method

X-RAY DIFFRACTION (3.705 Å)