Quaternary structure analysis of IRE1

Abstract

IRE1 belongs to a type I transmembrane protein family harboring two functional domains, cytoplasmic domain with kinase and RNAse catalytic activity, and the luminal domain, which is involved in the sensing of unfolded proteins. IRE1 molecule undergoes dimerization in the lumenal domain, which functionally activates the catalytic C-terminal domain. IRE1 activation is directly related to transition between monomeric and dimeric forms. We have deduced two quaternary structures from the published crystal structure of IRE1. One structure with a large stable interface that requires large activation and deactivation energy to active IRE1. The other quaternary structure has low dissociation energy and is more suitable for IRE1 oligomeric transition.

Figure 1. Quaternary structural analysis of IRE1

A. Quaternary structure form of lumenal domain of IRE1 (PDB ID: 2HZ6). The more stable form of quaternary structure of IRE1 with 62.8 Å (wrongly labelled as 52.8 Å) end-to-end distance between C-termini of monomers. Distance between the C-terminal end are depicted with a dashed line. B . Quaternary structure form of lumenal domain of IRE1 (PDB ID: 2HZ6) showing alternative arrangement of a dimer. Less stable form with 42.8 Å end-to-end distance between C-termini of monomers. Distance between the C-terminal end are depicted with a dashed line.