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Updated: Aug 2, 2025

Electrophoretic Mobility Shift Assay EMSA for the Study of RNA-Protein Interactions: The IRE/IRP Example

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Published on: December 3, 2014

Quaternary structure analysis of IRE1.

Samirul Bashir¹, Debnath Pal², Ozaira Qadri¹

¹University of Kashmir, Srinagar, Jammu and Kashmir, India.

Micropublication Biology

|April 17, 2023

Summary

Inositol-requiring enzyme 1 (IRE1) activation depends on its transition between monomeric and dimeric forms. Two quaternary structures were identified, with one being more suitable for IRE1 oligomeric transition.

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Area of Science:

Molecular biology
Cellular signaling
Protein structure

Background:

Inositol-requiring enzyme 1 (IRE1) is a type I transmembrane protein crucial for the unfolded protein response.
IRE1 possesses cytoplasmic kinase and RNase catalytic domains and a luminal domain for sensing unfolded proteins.
IRE1 activation is mediated by dimerization in the luminal domain, which activates its C-terminal catalytic domain.

Purpose of the Study:

To investigate the quaternary structures of IRE1.
To understand the structural basis of IRE1 activation and oligomeric transitions.
To identify structural features that facilitate or hinder IRE1 functional state changes.

Main Methods:

Analysis of published crystal structures of IRE1.
Deduction of quaternary structures based on structural data.
Computational modeling of protein interfaces and transition energies.

Main Results:

Two distinct quaternary structures of IRE1 were identified.
One structure features a large, stable interface requiring significant energy for activation/deactivation.
The second structure exhibits low dissociation energy, favoring IRE1 oligomeric transitions.

Conclusions:

IRE1's quaternary structure significantly influences its activation dynamics.
The low dissociation energy structure is more conducive to the dynamic oligomeric transitions required for IRE1 function.
Understanding these structures provides insights into the regulation of the unfolded protein response.