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[[Image:1dt7.gif|left|200px]]<br /><applet load="1dt7" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1dt7" />
'''SOLUTION STRUCTURE OF THE C-TERMINAL NEGATIVE REGULATORY DOMAIN OF P53 IN A COMPLEX WITH CA2+-BOUND S100B(BB)'''<br />


==Overview==
==SOLUTION STRUCTURE OF THE C-TERMINAL NEGATIVE REGULATORY DOMAIN OF P53 IN A COMPLEX WITH CA2+-BOUND S100B(BB)==
A Ca2+ dependent conformational change in dimeric S100B(betabeta) is required for it to bind p53 and inhibit phosphorylation of this tumor suppressor in its C-terminal negative regulatory domain. A peptide derived from this region of p53 (residues 367-388) was found to have no regular structure in its native form by NMR spectroscopy, but becomes helical when bound to Ca2+ loaded S100B(betabeta). The three-dimensional structure of this complex reveals several favorable hydrophobic and electrostatic interactions between S100B(betabeta) and the p53 peptide in the binding pocket, where S100B(betabeta) sterically blocks sites of phosphorylation and acetylation on p53 that are important for transcription activation.
<StructureSection load='1dt7' size='340' side='right'caption='[[1dt7]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1dt7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DT7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DT7 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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=1dt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dt7 OCA], [https://pdbe.org/1dt7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dt7 RCSB], [https://www.ebi.ac.uk/pdbsum/1dt7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dt7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/S100B_RAT S100B_RAT] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization.<ref>PMID:19910580</ref> <ref>PMID:20351179</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/dt/1dt7_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=1dt7 ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Colorectal cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Hepatocellular carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Histiocytoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Li-Fraumeni syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Multiple malignancy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Nasopharyngeal carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Osteosarcoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Pancreatic cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Thyroid carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]]
*[[S100 proteins 3D structures|S100 proteins 3D structures]]
 
== References ==
==About this Structure==
<references/>
1DT7 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DT7 OCA].
__TOC__
 
</StructureSection>
==Reference==
[[Category: Homo sapiens]]
Structure of the negative regulatory domain of p53 bound to S100B(betabeta)., Rustandi RR, Baldisseri DM, Weber DJ, Nat Struct Biol. 2000 Jul;7(7):570-4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10876243 10876243]
[[Category: Large Structures]]
[[Category: Protein complex]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Baldisseri, D M.]]
[[Category: Baldisseri DM]]
[[Category: Rustandi, R R.]]
[[Category: Rustandi RR]]
[[Category: Weber, D J.]]
[[Category: Weber DJ]]
[[Category: CA]]
[[Category: c-terminal domain of p53]]
[[Category: calcium-binding]]
[[Category: ef-hand]]
[[Category: four helix bundle]]
[[Category: helix loop helix]]
[[Category: nmr]]
[[Category: p53]]
[[Category: s100 protein]]
[[Category: s100b]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:20:11 2008''

Latest revision as of 12:53, 20 March 2024

SOLUTION STRUCTURE OF THE C-TERMINAL NEGATIVE REGULATORY DOMAIN OF P53 IN A COMPLEX WITH CA2+-BOUND S100B(BB)SOLUTION STRUCTURE OF THE C-TERMINAL NEGATIVE REGULATORY DOMAIN OF P53 IN A COMPLEX WITH CA2+-BOUND S100B(BB)

Structural highlights

1dt7 is a 4 chain structure with sequence from Homo sapiens and Rattus norvegicus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

S100B_RAT Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization.[1] [2]

Evolutionary Conservation

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

See Also

References

  1. ↑ Tsoporis JN, Izhar S, Leong-Poi H, Desjardins JF, Huttunen HJ, Parker TG. S100B interaction with the receptor for advanced glycation end products (RAGE): a novel receptor-mediated mechanism for myocyte apoptosis postinfarction. Circ Res. 2010 Jan 8;106(1):93-101. doi: 10.1161/CIRCRESAHA.109.195834. Epub 2009, Nov 12. PMID:19910580 doi:10.1161/CIRCRESAHA.109.195834
  2. ↑ Gilquin B, Cannon BR, Hubstenberger A, Moulouel B, Falk E, Merle N, Assard N, Kieffer S, Rousseau D, Wilder PT, Weber DJ, Baudier J. The calcium-dependent interaction between S100B and the mitochondrial AAA ATPase ATAD3A and the role of this complex in the cytoplasmic processing of ATAD3A. Mol Cell Biol. 2010 Jun;30(11):2724-36. doi: 10.1128/MCB.01468-09. Epub 2010 Mar , 29. PMID:20351179 doi:10.1128/MCB.01468-09
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