Structural and functional basis for RNA cleavage by Ire1.

Citation data:

BMC biology, ISSN: 1741-7007, Vol: 9, Issue: 1, Page: 47

Publication Year:
2011
Usage 212
Abstract Views 136
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Citations 29
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Repository URL:
https://escholarship.umassmed.edu/oapubs/2266
PMID:
21729333
DOI:
10.1186/1741-7007-9-47
PMCID:
PMC3149027
Author(s):
Korennykh, Alexei V.; Korostelev, Andrei A.; Egea, Pascal F.; Finer-Moore, Janet; Stroud, Robert M.; Zhang, Chao; Shokat, Kevan M.; Walter, Peter
Publisher(s):
Springer Nature
Tags:
Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Endoribonucleases; Membrane Glycoproteins; Protein-Serine-Threonine Kinases; RNA Cleavage; Saccharomyces cerevisiae Proteins; Unfolded Protein Response; Biochemistry, Biophysics, and Structural Biology; Life Sciences; Medicine and Health Sciences
article description
The unfolded protein response (UPR) controls the protein folding capacity of the endoplasmic reticulum (ER). Central to this signaling pathway is the ER-resident bifunctional transmembrane kinase/endoribonuclease Ire1. The endoribonuclease (RNase) domain of Ire1 initiates a non-conventional mRNA splicing reaction, leading to the production of a transcription factor that controls UPR target genes. The mRNA splicing reaction is an obligatory step of Ire1 signaling, yet its mechanism has remained poorly understood due to the absence of substrate-bound crystal structures of Ire1, the lack of structural similarity between Ire1 and other RNases, and a scarcity of quantitative enzymological data. Here, we experimentally define the active site of Ire1 RNase and quantitatively evaluate the contribution of the key active site residues to catalysis.