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5zk1

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Revision as of 21:20, 28 October 2020

Crystal Structure of the CRTC2(SeMet)-CREB-CRE complex

Structural highlights

5zk1 is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CREB1_HUMAN] Melanoma of soft part. Angiomatoid fibrous histiocytoma (AFH) [MIM: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

[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).^[1] ^[2] [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.

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^[3]

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

References

↑ Koo SH, Flechner L, Qi L, Zhang X, Screaton RA, Jeffries S, Hedrick S, Xu W, Boussouar F, Brindle P, Takemori H, Montminy M. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature. 2005 Oct 20;437(7062):1109-11. doi: 10.1038/nature03967. Epub 2005 Sep 7. PMID:16148943 doi:http://dx.doi.org/10.1038/nature03967
↑ Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M, Cantley LC. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005 Dec 9;310(5754):1642-6. Epub 2005 Nov 24. PMID:16308421 doi:http://dx.doi.org/1120781
↑ Song Y, Zhai L, Valencia Swain J, Chen Y, Wang P, Chen L, Liu Y, Xiang S. Structural Insights into the CRTC2-CREB Complex Assembly on CRE. J Mol Biol. 2018 Jun 22;430(13):1926-1939. doi: 10.1016/j.jmb.2018.04.038. Epub, 2018 May 4. PMID:29733854 doi:http://dx.doi.org/10.1016/j.jmb.2018.04.038

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5zk1"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the CRTC2(SeMet)-CREB-CRE complex==
-<StructureSection load='5zk1' size='340' side='right' caption='[[5zk1]], [[Resolution|resolution]] 3.05&Aring;' scene=''>
+<StructureSection load='5zk1' size='340' side='right'caption='[[5zk1]], [[Resolution|resolution]] 3.05&Aring;' 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>
+<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://proteopedia.org/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>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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 ==
@@ Line 21: / Line 21: @@
 </div>
 <div class="pdbe-citations 5zk1" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Valencia-Swain, J]]
 [[Category: Xiang, S]]

5zk1

From Proteopedia

Revision as of 21:20, 28 October 2020

Crystal Structure of the CRTC2(SeMet)-CREB-CRE complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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