1hu8

From Proteopedia

(Difference between revisions)

Revision as of 10:33, 18 November 2020

CRYSTAL STRUCTURE OF THE MOUSE P53 CORE DNA-BINDING DOMAIN AT 2.7A RESOLUTION

Structural highlights

1hu8 is a 3 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	P53 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[P53_MOUSE] Note=p53 is found in increased amounts in a wide variety of transformed cells. p53 is frequently mutated or inactivated in many types of cancer.

Function

[P53_MOUSE] Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent of transcription. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression (By similarity). Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis, but seems to have to effect on cell-cycle regulation.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The p53 tumor suppressor is a sequence-specific DNA-binding protein that activates transcription in response to DNA damage to promote cell cycle arrest or apoptosis. The p53 protein functions in a tetrameric form in vivo and contains four domains including an N-terminal transcriptional activation domain, a C-terminal regulatory domain, a tetramerization domain, and a central core DNA-binding domain that is the site of the majority of tumor-derived mutations. Here we report the 2.7-A crystal structure of the mouse p53 core domain. Like the human p53 core domain in complex with DNA, the mouse p53 core domain adopts an immunoglobulin-like beta sandwich architecture with a series of loops and short helices at opposite ends of the beta sandwich. Comparison of the DNA-bound and DNA-free p53 core domains reveals that while the central beta sandwich architecture remains largely unchanged, a loop region important for DNA binding undergoes significant rearrangement. Although this loop region mediates major groove DNA contacts in the DNA-bound structure, it adopts a conformation that is incompatible with DNA binding in the DNA-free structure. Interestingly, crystals of the DNA-free core domain contain a noncrystallographic trimer with three nearly identical subunit-subunit (dimer) contacts. These dimer contacts align the p53 core domains in a way that is incompatible with simultaneous DNA binding by both protomers of the dimer. Surprisingly, similar dimer contacts are observed in crystals of the human p53 core domain with DNA in which only one of the three p53 protomers in the asymmetric unit cell is specifically bound to DNA. We propose that the p53 core domain dimer that is seen in the crystals described here represents a physiologically relevant inactive form of p53 that must undergo structural rearrangement for sequence-specific DNA binding.

Crystal structure of the mouse p53 core DNA-binding domain at 2.7 A resolution.,Zhao K, Chai X, Johnston K, Clements A, Marmorstein R J Biol Chem. 2001 Apr 13;276(15):12120-7. Epub 2001 Jan 4. PMID:11152481^[4]

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

References

↑ Allton K, Jain AK, Herz HM, Tsai WW, Jung SY, Qin J, Bergmann A, Johnson RL, Barton MC. Trim24 targets endogenous p53 for degradation. Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11612-6. doi:, 10.1073/pnas.0813177106. Epub 2009 Jun 25. PMID:19556538 doi:10.1073/pnas.0813177106
↑ Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010 Aug 6;142(3):409-19. doi: 10.1016/j.cell.2010.06.040. PMID:20673990 doi:10.1016/j.cell.2010.06.040
↑ Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell. 2012 Jun 22;149(7):1536-48. doi: 10.1016/j.cell.2012.05.014. PMID:22726440 doi:10.1016/j.cell.2012.05.014
↑ Zhao K, Chai X, Johnston K, Clements A, Marmorstein R. Crystal structure of the mouse p53 core DNA-binding domain at 2.7 A resolution. J Biol Chem. 2001 Apr 13;276(15):12120-7. Epub 2001 Jan 4. PMID:11152481 doi:10.1074/jbc.M011644200

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1hu8"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF THE MOUSE P53 CORE DNA-BINDING DOMAIN AT 2.7A RESOLUTION==
-<StructureSection load='1hu8' size='340' side='right' caption='[[1hu8]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='1hu8' size='340' side='right'caption='[[1hu8]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1hu8]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HU8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1hu8]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HU8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1HU8 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">P53 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=1hu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hu8 OCA], [http://pdbe.org/1hu8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hu8 RCSB], [http://www.ebi.ac.uk/pdbsum/1hu8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1hu8 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=1hu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hu8 OCA], [http://pdbe.org/1hu8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hu8 RCSB], [http://www.ebi.ac.uk/pdbsum/1hu8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1hu8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 31: @@
 </div>
 <div class="pdbe-citations 1hu8" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[P53 3D structures|P53 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Chai, X]]

1hu8

From Proteopedia

Revision as of 10:33, 18 November 2020

CRYSTAL STRUCTURE OF THE MOUSE P53 CORE DNA-BINDING DOMAIN AT 2.7A RESOLUTION

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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