5zk1
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Crystal Structure of the CRTC2(SeMet)-CREB-CRE complex== |
| + | <StructureSection load='5zk1' size='340' side='right' caption='[[5zk1]], [[Resolution|resolution]] 3.05Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5zk1]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZK1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZK1 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=5zk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zk1 OCA], [http://pdbe.org/5zk1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zk1 RCSB], [http://www.ebi.ac.uk/pdbsum/5zk1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zk1 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/CREB1_HUMAN CREB1_HUMAN]] Melanoma of soft part. Angiomatoid fibrous histiocytoma (AFH) [MIM:[http://omim.org/entry/612160 612160]]: A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. Note=The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving CREB1 is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type. Note=A CREB1 mutation has been found in a patient with multiple congenital anomalies consisting of agenesis of the corpus callosum, cerebellar hypoplasia, severe neonatal respiratory distress refractory to surfactant, thymus hypoplasia, and thyroid follicular hypoplasia (PubMed:22267179). | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/CRTC2_MOUSE CRTC2_MOUSE]] Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling pathway. Regulates the expression of specific genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells (By similarity).<ref>PMID:16148943</ref> <ref>PMID:16308421</ref> [[http://www.uniprot.org/uniprot/CREB1_HUMAN CREB1_HUMAN]] Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The cAMP response element (CRE) binding protein (CREB) is central in the transcription regulation by cAMP, and the CREB-regulated transcriptional coactivators (CRTCs) play critical roles in CREB-mediated transcription activation. Upon stimulation, CRTCs translocate into the nucleus and complex with CREB on CRE promoters to activate target gene transcription. Their physiological importance is underscored by their function in energy balance, long-term memory, longevity and other processes. The CREB binding domain on CRTCs has been mapped, which interacts with the CREB basic leucine zipper domain that also mediates interaction with CRE-containing DNA. We report here crystal structures of a complex containing the CRTC2 CREB binding domain, the CREB basic leucine zipper domain and a CRE-containing DNA. The structures revealed that CRTC and CREB form a 2:2 complex on CRE-containing DNA, and CRTC interacts with both CREB and DNA through highly conserved residues. Structure-guided functional studies revealed that both interactions are crucial for the complex assembly and CREB stabilization on DNA. Interestingly, we found that the CRTC-DNA interaction confers selectivity toward the intrinsic DNA shape, which may play a role in selective transcription activation of the CRE genes. | ||
| - | + | Structural Insights into the CRTC2-CREB Complex Assembly on CRE.,Song Y, Zhai L, Valencia Swain J, Chen Y, Wang P, Chen L, Liu Y, Xiang S J Mol Biol. 2018 Jun 22;430(13):1926-1939. doi: 10.1016/j.jmb.2018.04.038. Epub, 2018 May 4. PMID:29733854<ref>PMID:29733854</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5zk1" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Valencia-Swain, J]] | [[Category: Valencia-Swain, J]] | ||
| + | [[Category: Xiang, S]] | ||
| + | [[Category: Zhai, L]] | ||
| + | [[Category: Co-activator]] | ||
| + | [[Category: Cre]] | ||
| + | [[Category: Creb]] | ||
| + | [[Category: Crtc]] | ||
| + | [[Category: Transcription factor]] | ||
| + | [[Category: Transcription-dna complex]] | ||
Revision as of 05:45, 20 June 2018
Crystal Structure of the CRTC2(SeMet)-CREB-CRE complex
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