A conserved structural determinant located at the interdomain region of mammalian inositol-requiring enzyme 1alpha.

ABSTRACT: Inositol-requiring enzyme 1α (IRE1α), an endoplasmic reticulum-resident sensor for mammalian unfolded protein response, is a bifunctional enzyme containing kinase and RNase domains critical for trans-autophosphorylation and Xbp1 mRNA splicing, respectively, in response to endoplasmic reticulum stress. However, the amino acid residues important for its function and activation remain largely unexplored. Here, through analysis of IRE1α mutants associated with human somatic cancers, we have identified a highly conserved proline residue at position 830 (Pro(830)) that is critical for its structural integrity and hence, the activation of both kinase and RNase domains. Structural analysis revealed that Pro(830) may form a highly conserved structural linker with adjacent tryptophan and tyrosine re

SUBMITTER: Xue Z 

PROVIDER: S-EPMC3162446 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature