5bvi

X-ray Structure of Interferon Regulatory Factor 4 IAD DomainX-ray Structure of Interferon Regulatory Factor 4 IAD Domain

Structural highlights

5bvi is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IRF4_MOUSE Transcriptional activator. Binds to the interferon-stimulated response element (ISRE) of the MHC class I promoter. Binds the immunoglobulin lambda light chain enhancer, together with PU.1. Probably plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 and activation of genes.^[1] ^[2] ^[3]

Publication Abstract from PubMed

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 beta-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.

Structural Studies of IRF4 Reveal a Flexible Autoinhibitory Region and a Compact Linker Domain.,Remesh SG, Santosh V, Escalante CR J Biol Chem. 2015 Sep 24. pii: jbc.M115.678789. PMID:26405037^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Glasmacher E, Agrawal S, Chang AB, Murphy TL, Zeng W, Vander Lugt B, Khan AA, Ciofani M, Spooner CJ, Rutz S, Hackney J, Nurieva R, Escalante CR, Ouyang W, Littman DR, Murphy KM, Singh H. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science. 2012 Nov 16;338(6109):975-80. PMID:22983707 doi:10.1126/science.1228309
↑ Li P, Spolski R, Liao W, Wang L, Murphy TL, Murphy KM, Leonard WJ. BATF-JUN is critical for IRF4-mediated transcription in T cells. Nature. 2012 Oct 25;490(7421):543-6. PMID:22992523 doi:10.1038/nature11530
↑ Tussiwand R, Lee WL, Murphy TL, Mashayekhi M, KC W, Albring JC, Satpathy AT, Rotondo JA, Edelson BT, Kretzer NM, Wu X, Weiss LA, Glasmacher E, Li P, Liao W, Behnke M, Lam SS, Aurthur CT, Leonard WJ, Singh H, Stallings CL, Sibley LD, Schreiber RD, Murphy KM. Compensatory dendritic cell development mediated by BATF-IRF interactions. Nature. 2012 Oct 25;490(7421):502-7. PMID:22992524 doi:10.1038/nature11531
↑ Remesh SG, Santosh V, Escalante CR. Structural Studies of IRF4 Reveal a Flexible Autoinhibitory Region and a Compact Linker Domain. J Biol Chem. 2015 Sep 24. pii: jbc.M115.678789. PMID:26405037 doi:http://dx.doi.org/10.1074/jbc.M115.678789

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OCA

[1] Glasmacher E, Agrawal S, Chang AB, Murphy TL, Zeng W, Vander Lugt B, Khan AA, Ciofani M, Spooner CJ, Rutz S, Hackney J, Nurieva R, Escalante CR, Ouyang W, Littman DR, Murphy KM, Singh H. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science. 2012 Nov 16;338(6109):975-80. PMID:22983707 doi:10.1126/science.1228309

[2] Li P, Spolski R, Liao W, Wang L, Murphy TL, Murphy KM, Leonard WJ. BATF-JUN is critical for IRF4-mediated transcription in T cells. Nature. 2012 Oct 25;490(7421):543-6. PMID:22992523 doi:10.1038/nature11530

[3] Tussiwand R, Lee WL, Murphy TL, Mashayekhi M, KC W, Albring JC, Satpathy AT, Rotondo JA, Edelson BT, Kretzer NM, Wu X, Weiss LA, Glasmacher E, Li P, Liao W, Behnke M, Lam SS, Aurthur CT, Leonard WJ, Singh H, Stallings CL, Sibley LD, Schreiber RD, Murphy KM. Compensatory dendritic cell development mediated by BATF-IRF interactions. Nature. 2012 Oct 25;490(7421):502-7. PMID:22992524 doi:10.1038/nature11531

[4] Remesh SG, Santosh V, Escalante CR. Structural Studies of IRF4 Reveal a Flexible Autoinhibitory Region and a Compact Linker Domain. J Biol Chem. 2015 Sep 24. pii: jbc.M115.678789. PMID:26405037 doi:http://dx.doi.org/10.1074/jbc.M115.678789

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