2hz6
From Proteopedia
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The crystal structure of human IRE1-alpha luminal domain
Overview
The unfolded protein response (UPR) is an evolutionarily conserved, mechanism by which all eukaryotic cells adapt to the accumulation of, unfolded proteins in the endoplasmic reticulum (ER). Inositol-requiring, kinase 1 (IRE1) and PKR-related ER kinase (PERK) are two type I, transmembrane ER-localized protein kinase receptors that signal the UPR, through a process that involves homodimerization and autophosphorylation., To elucidate the molecular basis of the ER transmembrane signaling event, we determined the x-ray crystal structure of the luminal domain of human, IRE1alpha. The monomer of the luminal domain comprises a unique fold of a, triangular assembly of beta-sheet clusters. Structural analysis identified, an extensive dimerization interface stabilized by hydrogen bonds and, hydrophobic interactions. Dimerization creates an MHC-like groove at the, interface. However, because this groove is too narrow for peptide binding, and the purified luminal domain forms high-affinity dimers in vitro, peptide binding to this groove is not required for dimerization., Consistent with our structural observations, mutations that disrupt the, dimerization interface produced IRE1alpha molecules that failed to either, dimerize or activate the UPR upon ER stress. In addition, mutations in a, structurally homologous region within PERK also prevented dimerization., Our structural, biochemical, and functional studies in vivo altogether, demonstrate that IRE1 and PERK have conserved a common molecular interface, necessary and sufficient for dimerization and UPR signaling.
About this Structure
2HZ6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of human IRE1 luminal domain reveals a conserved dimerization interface required for activation of the unfolded protein response., Zhou J, Liu CY, Back SH, Clark RL, Peisach D, Xu Z, Kaufman RJ, Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14343-8. Epub 2006 Sep 14. PMID:16973740
Page seeded by OCA on Wed Nov 21 12:03:48 2007
