2rio | pdb_00002rio

File:2rio.jpg

spinqualitylabelsall models 2rio, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation of non-conventional splicing

Overview

Ire1 is an ancient transmembrane sensor of ER stress with dual protein kinase and ribonuclease activities. In response to ER stress, Ire1 catalyzes the splicing of target mRNAs in a spliceosome-independent manner. We have determined the crystal structure of the dual catalytic region of Ire1at 2.4 A resolution, revealing the fusion of a domain, which we term the KEN domain, to the protein kinase domain. Dimerization of the kinase domain composes a large catalytic surface on the KEN domain which carries out ribonuclease function. We further show that signal induced trans-autophosphorylation of the kinase domain permits unfettered binding of nucleotide, which in turn promotes dimerization to compose the ribonuclease active site. Comparison of Ire1 to a topologically disparate ribonuclease reveals the convergent evolution of their catalytic mechanism. These findings provide a basis for understanding the mechanism of action of RNaseL and other pseudokinases, which represent 10% of the human kinome.

About this Structure

2RIO is a Single protein structure of sequence from Saccharomyces cerevisiae with MG, SR and ADP as ligands. Known structural/functional Sites: AC1, AC2, AC3, AC4, AC5 and AC6. Full crystallographic information is available from OCA.

Reference

Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing., Lee KP, Dey M, Neculai D, Cao C, Dever TE, Sicheri F, Cell. 2008 Jan 11;132(1):89-100. PMID:18191223

Page seeded by OCA on Thu Feb 21 18:47:38 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA