title: Structural Studies of IRF4 Reveal a Flexible Autoinhibitory Region and a Compact Linker Domain.
abstract: IRF4 is a unique member of the interferon regulatory factor (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 small angle x-ray scattering studies, we reveal unique features of the interferon activation domain, 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 small angle x-ray scattering solution structure of full-length IRF4, which, together with circular dichroism studies, suggests that the linker region is not extended but folds into a domain structure.
authors.affiliation: From the Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia 23298.
authors.forename: Soumya G
authors.initials: SG
authors.lastname: Remesh
authors.affiliation: From the Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia 23298.
authors.forename: Vishaka
authors.initials: V
authors.lastname: Santosh
authors.affiliation: From the Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia 23298 cescalante@vcu.edu.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Escalante
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D050835:Interferon Regulatory Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D000099218:Interferon Regulatory Factor-4
keywords: gene regulation; interferon regulatory factor (IRF); small angle x-ray scattering (SAXS); structural biology; transcription factor; x-ray crystallography