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New page: left|200px<br /><applet load="2ram" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ram, resolution 2.40Å" /> '''A NOVEL DNA RECOGNIT...
 
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[[Image:2ram.jpg|left|200px]]<br /><applet load="2ram" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2ram, resolution 2.40&Aring;" />
'''A NOVEL DNA RECOGNITION MODE BY NF-KB P65 HOMODIMER'''<br />


==Overview==
==A NOVEL DNA RECOGNITION MODE BY NF-KB P65 HOMODIMER==
The crystal structure of the NF-kappa B p65 (RelA) homodimer in complex, with a DNA target has been determined to 2.4 A resolution. The two p65, subunits are not symmetrically disposed on the DNA target. The homodimer, should optimally bind to a pseudo-palindromic nine base pair target with, each subunit recognizing a 5'GGAA-3' half site separated by a central A-T, base pair. However, one of the subunits (subunit B) encounters a half site, of 5'-GAAA-3'. The single base-pair change from G-C to A-T results in, highly unfavorable interactions between this half site and the base, contacting protein residues in subunit B, which leads to an 18 degrees, rotation of the N-terminal terminal domain from its normal conformation., Remarkably, subunit B retains all the interactions with the sugar, phosphate backbone of the DNA target. This mode of interaction allows the, NF-kappa B p65 homodimer to recognize DNA targets containing only one, cognate half site. Differences in the sequence of the other half site, provide variations in conformation and affinity of the complex.
<StructureSection load='2ram' size='340' side='right'caption='[[2ram]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ram]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RAM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RAM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5IU:5-IODO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>5IU</scene>, <scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</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=2ram FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ram OCA], [https://pdbe.org/2ram PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ram RCSB], [https://www.ebi.ac.uk/pdbsum/2ram PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ram ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TF65_MOUSE TF65_MOUSE] NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression (By similarity). The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1.<ref>PMID:21131967</ref> <ref>PMID:22244329</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/ra/2ram_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=2ram ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2RAM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with DTV as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2RAM OCA].
*[[NF-kB|NF-kB]]
 
== References ==
==Reference==
<references/>
A novel DNA recognition mode by the NF-kappa B p65 homodimer., Chen YQ, Ghosh S, Ghosh G, Nat Struct Biol. 1998 Jan;5(1):67-73. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9437432 9437432]
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: Chen YQ]]
[[Category: Chen, Y.Q.]]
[[Category: Ghosh G]]
[[Category: Ghosh, G.]]
[[Category: Ghosh S]]
[[Category: Ghosh, S.]]
[[Category: DTV]]
[[Category: activator nuclear protein]]
[[Category: complex (transcription factor/dna)]]
[[Category: conformation]]
[[Category: dna-binding]]
[[Category: phosphorylation]]
[[Category: transcription regulation]]
 
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Retrieved from "https://proteopedia.org/2ram"