2020年10月15日 · Experimental evidence suggests that IRE1 forms several three dimensional (3D) structural variants: dimers, tetramers and higher order oligomers, where each structural variant can contain...

2022年6月22日 · Applying this approach to a key regulator of cellular proteostasis, IRE1, we demonstrated that the dimer-to-oligomer transition serves as the primary regulatory step in enzymatic activation, and reinforced the role of the lumenal domain as the master governor of IRE1’s oligomeric state.

2020年12月14日 · Excess unfolded proteins in the ER lumen induce dimerization and oligomerization of IRE1, triggering kinase trans-autophosphorylation and RNase activation. Known ATP-competitive small-molecule...

2022年1月1日 · The findings herein, showing the existence and activity of IRE1 dimer disruptors, opens for an entirely new mode of action to block the UPR, and can serve as an additional and viable route to trigger apoptosis or sensitize cells in adjuvant therapies also including e.g. a cytotoxic compound.

2008年1月11日 · IRE1-mediated cleavage of HAC1 mRNA depends on its kinase activity—only wild-type kinase-active IRE1 is able to cleave its mRNA substrate in vitro. ER stress promotes IRE1 dimerization, which facilitates trans-autophosphorylation and kinase activation.

2003年5月16日 · IRE1α is a type-I transmembrane glycoprotein for which the N-terminal luminal domain (NLD) senses the accumulation of unfolded proteins. Previously we demonstrated that the NLD forms a stable ligand-independent dimer linked by disulfide bridges.

IRE1 transduces the unfolded protein response by splicing XBP1 through its C-terminal cytoplasmic kinase-RNase region. IRE1 autophosphorylation is coupled to RNase activity through formation of a back-to-back dimer, although the conservation of the underlying molecular mechanism is not clear from existing structures.

2006年9月26日 · Structure of the IRE1 NLD Dimer. The NLD forms stable dimers in vitro with an apparent molecular mass of 96 kDa ( 24 ). Because the asymmetric unit of the crystal contains only one monomer, the dimer interface must span the crystallographic symmetry axis.

We have now determined the crystal structure of the cytoplasmic kinase-RNase region of human Ire1α at 2.7 Å resolution, in a dephosphorylated state, and in a complex with Mg 2+-ADP, revealing a face-to-face dimer of the kinase domains, reminiscent of dimerisation-activated kinases such as Chk2, LOK, SLK, and DAPK3 (Oliver et al, 2006, 2007 ...

2008年12月14日 · A recent crystal structure of the kinase/RNase domain of Ire1 reveals a two-fold symmetric dimer with a back-to-back arrangement of the kinase domains, compactly attached to an RNase dimer ...