2rio

From Proteopedia

Revision as of 09:00, 31 January 2008

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 , and as ligands. Known structural/functional Sites: , , , , and . 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

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