Structural Studies of IRF4 Reveal a Flexible Autoinhibitory Region and a Compact Linker Domain [Gene Regulation]

September 24th, 2015 by Remesh, S. G., Santosh, V., Escalante, C. R.

IRF4 is a unique member of the IRF family playing critical regulatory roles in immune cell development, regulation of obesity-induced inflammation and control of thermogenic gene expression. The ability of IRF4 to control diverse transcriptional programs arises from its proficiency to interact with numerous transcriptional partners. In this study we present the structural characterization of full length IRF4. Using a combination of X-ray and SAXS studies, we reveal unique features of the Interferon Activation Domain (IAD) including a set of β-sheets and loops that serve as the binding site for PU.1 and also show that unlike other IRF members, IRF4 has a flexible autoinhibitory region. In addition, we have determined the SAXS solution structure of full length IRF4 that together with circular dichroism studies suggest that the linker region is not extended but folds into a domain structure.