View source for 3dsh

==Crystal structure of dimeric interferon regulatory factor 5 (IRF-5) transactivation domain==
<StructureSection load='3dsh' size='340' side='right' caption='[[3dsh]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3dsh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DSH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DSH FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IRF5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dsh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dsh OCA], [http://pdbe.org/3dsh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dsh RCSB], [http://www.ebi.ac.uk/pdbsum/3dsh PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/IRF5_HUMAN IRF5_HUMAN]] Genetic variations in IRF5 are associated with susceptibility to inflammatory bowel disease type 14 (IBD14) [MIM:[http://omim.org/entry/612245 612245]]. IBD14 is a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.<ref>PMID:17881657</ref>   Genetic variations in IRF5 are associated with susceptibility to systemic lupus erythematosus type 10 (SLEB10) [MIM:[http://omim.org/entry/612251 612251]]. Systemic lupus erythematosus (SLE) is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.  Genetic variations in IRF5 are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:[http://omim.org/entry/180300 180300]]. It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. 
== Function ==
[[http://www.uniprot.org/uniprot/IRF5_HUMAN IRF5_HUMAN]] Transcription factor involved in the induction of interferons IFNA and INFB and inflammatory cytokines upon virus infection. Activated by TLR7 or TLR8 signaling.<ref>PMID:11303025</ref> <ref>PMID:15695821</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ds/3dsh_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3dsh ConSurf].
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== Publication Abstract from PubMed ==
Interferon regulatory factors (IRFs) are essential in the innate immune response and other physiological processes. Activation of these proteins in the cytoplasm is triggered by phosphorylation of serine and threonine residues in a C-terminal autoinhibitory region, which stimulates dimerization, transport into the nucleus, assembly with the coactivator CBP/p300 and initiation of transcription. The crystal structure of the transactivation domain of pseudophosphorylated human IRF5 strikingly reveals a dimer in which the bulk of intersubunit interactions involve a highly extended C-terminal region. The corresponding region has previously been shown to block CBP/p300 binding to unphosphorylated IRF3. Mutation of key interface residues supports the observed dimer as the physiologically activated state of IRF5 and IRF3. Thus, phosphorylation is likely to activate IRF5 and other family members by triggering conformational rearrangements that switch the C-terminal segment from an autoinihibitory to a dimerization role.

Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5.,Chen W, Lam SS, Srinath H, Jiang Z, Correia JJ, Schiffer CA, Fitzgerald KA, Lin K, Royer WE Jr Nat Struct Mol Biol. 2008 Nov;15(11):1213-20. Epub 2008 Oct 5. PMID:18836453<ref>PMID:18836453</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3dsh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Interferon regulatory factor|Interferon regulatory factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Chen, W]]
[[Category: Correia, J J]]
[[Category: Fitzgerald, K A]]
[[Category: Jiang, Z]]
[[Category: Lam, S S]]
[[Category: Lin, K]]
[[Category: Royer, W E]]
[[Category: Schiffer, C]]
[[Category: Srinath, H]]
[[Category: Dna binding protein]]
[[Category: Dna-binding]]
[[Category: Nucleus]]
[[Category: Phosphoactivation induced dimerization]]
[[Category: Transcription]]
[[Category: Transcription regulation]]