2RIO

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

Summary for 2RIO

• Entry DOI: 10.2210/pdb2rio/pdb
• Descriptor: Serine/threonine-protein kinase/endoribonuclease IRE1, MAGNESIUM ION, STRONTIUM ION, ... (4 entities in total)
• Functional Keywords: protein-nucleotide complex, atp-binding, endoplasmic reticulum, glycoprotein, hydrolase, kinase, magnesium, membrane, metal-binding, multifunctional enzyme, nucleotide-binding, phosphorylation, serine/threonine-protein kinase, transcription, transcription regulation, transferase, transmembrane, unfolded protein response
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Cellular location: Endoplasmic reticulum membrane; Single-pass type I membrane protein: P32361
• Total number of polymer chains: 2
• Total formula weight: 101155.05

Authors

Lee, K.P.,Dey, M.,Neculai, D.,Cao, C.,Dever, T.E.,Sicheri, F. (deposition date: 2007-10-12, release date: 2008-01-29, Last modification date: 2024-02-21)

Primary citation

Lee, K.P.,Dey, M.,Neculai, D.,Cao, C.,Dever, T.E.,Sicheri, F.
Structure of the dual enzyme ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing.
Cell(Cambridge,Mass.), 132:89-100, 2008

PubMed Abstract: 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.

PubMed: 18191223
DOI: 10.1016/j.cell.2007.10.057

Experimental method

X-RAY DIFFRACTION (2.4 Å)