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| | ==Crystal structure of the CRTC2-CREB-CRE complex== | | ==Crystal structure of the CRTC2-CREB-CRE complex== |
| - | <StructureSection load='5zko' size='340' side='right' caption='[[5zko]], [[Resolution|resolution]] 3.05Å' scene=''> | + | <StructureSection load='5zko' size='340' side='right'caption='[[5zko]], [[Resolution|resolution]] 3.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zko]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZKO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZKO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zko]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZKO FirstGlance]. <br> |
| - | </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=5zko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zko OCA], [http://pdbe.org/5zko PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zko RCSB], [http://www.ebi.ac.uk/pdbsum/5zko PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zko ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.05Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5zko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zko OCA], [https://pdbe.org/5zko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zko RCSB], [https://www.ebi.ac.uk/pdbsum/5zko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zko ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == 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). | + | [https://www.uniprot.org/uniprot/CREB1_HUMAN CREB1_HUMAN] Melanoma of soft part. Angiomatoid fibrous histiocytoma (AFH) [MIM:[https://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 == | | == Function == |
| - | [[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. [[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> | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5zko" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5zko" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Valecia-Swain, J]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Xiang, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhai, L]] | + | [[Category: Mus musculus]] |
| - | [[Category: Coactivator]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Cre]] | + | [[Category: Valecia-Swain J]] |
| - | [[Category: Creb]] | + | [[Category: Xiang S]] |
| - | [[Category: Crtc]] | + | [[Category: Zhai L]] |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| - | [[Category: Transcription-dna complex]]
| + | |
| Structural highlights
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
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
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