7cli - Revision history

OCA at 09:22, 9 October 2024

2024-10-09T09:22:35Z

← Older revision		Revision as of 09:22, 9 October 2024
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	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7cli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cli OCA], [https://pdbe.org/7cli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cli RCSB], [https://www.ebi.ac.uk/pdbsum/7cli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cli ProSAT]</span></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=7cli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cli OCA], [https://pdbe.org/7cli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cli RCSB], [https://www.ebi.ac.uk/pdbsum/7cli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cli ProSAT]</span></td></tr>
	</table>		</table>
	~~== Disease ==~~
	[https://www.uniprot.org/uniprot/NFKB2_HUMAN NFKB2_HUMAN] Note=A chromosomal aberration involving NFKB2 is found in a case of B-cell non Hodgkin lymphoma (B-NHL). Translocation t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called Lyt-10C alpha variant. Note=A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which encodes for a truncated 80 kDa protein (p80HT). Note=In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions.
	~~== Function ==~~
	[https://www.uniprot.org/uniprot/NFKB2_HUMAN NFKB2_HUMAN] 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. 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. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65.<ref>PMID:7925301</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 16:10, 29 November 2023

2023-11-29T16:10:29Z

← Older revision		Revision as of 16:10, 29 November 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7cli]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CLI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CLI FirstGlance]. <br>		<table><tr><td colspan='2'>[[7cli]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CLI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CLI FirstGlance]. <br>
	</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=7cli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cli OCA], [https://pdbe.org/7cli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cli RCSB], [https://www.ebi.ac.uk/pdbsum/7cli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cli 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]] 3Å</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=7cli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cli OCA], [https://pdbe.org/7cli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cli RCSB], [https://www.ebi.ac.uk/pdbsum/7cli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cli ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 09:59, 15 March 2023

2023-03-15T09:59:02Z

← Older revision		Revision as of 09:59, 15 March 2023
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	====		==Structure of NF-kB p52 homodimer bound to P-Selectin kB DNA fragment==
	<StructureSection load='7cli' size='340' side='right'caption='[[7cli]]' scene=''>		<StructureSection load='7cli' size='340' side='right'caption='[[7cli]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>		<table><tr><td colspan='2'>[[7cli]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CLI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CLI FirstGlance]. <br>
	</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=7cli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cli OCA], [https://pdbe.org/7cli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cli RCSB], [https://www.ebi.ac.uk/pdbsum/7cli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cli ProSAT]</span></td></tr>		</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=7cli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cli OCA], [https://pdbe.org/7cli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cli RCSB], [https://www.ebi.ac.uk/pdbsum/7cli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cli ProSAT]</span></td></tr>
	</table>		</table>
			== Disease ==
			[https://www.uniprot.org/uniprot/NFKB2_HUMAN NFKB2_HUMAN] Note=A chromosomal aberration involving NFKB2 is found in a case of B-cell non Hodgkin lymphoma (B-NHL). Translocation t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called Lyt-10C alpha variant. Note=A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which encodes for a truncated 80 kDa protein (p80HT). Note=In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions.
			== Function ==
			[https://www.uniprot.org/uniprot/NFKB2_HUMAN NFKB2_HUMAN] 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. 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. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65.<ref>PMID:7925301</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The mammalian NF-kappaB p52:p52 homodimer together with its cofactor Bcl3 activates transcription of kappaB sites with a central G/C base pair (bp), while it is inactive toward kappaB sites with a central A/T bp. To understand the molecular basis for this unique property of p52, we have determined the crystal structures of recombinant human p52 protein in complex with a P-selectin(PSel)-kappaB DNA (5'-GGGGTGACCCC-3') (central bp is underlined) and variants changing the central bp to A/T or swapping the flanking bp. The structures reveal a nearly two-fold widened minor groove in the central region of the DNA as compared to all other currently available NF-kappaB-DNA complex structures, which have a central A/T bp. Microsecond molecular dynamics (MD) simulations of free DNAs and p52 bound complexes reveal that free DNAs exhibit distinct preferred conformations, and p52:p52 homodimer induces the least amount of DNA conformational changes when bound to the more transcriptionally active natural G/C-centric PSel-kappaB, but adopts closed conformation when bound to the mutant A/T and swap DNAs due to their narrowed minor grooves. Our binding assays further demonstrate that the fast kinetics favored by entropy is correlated with higher transcriptional activity. Overall, our studies have revealed a novel conformation for kappaB DNA in complex with NF-kappaB and pinpoint the importance of binding kinetics, dictated by DNA conformational and dynamic states, in controlling transcriptional activation for NF-kappaB.

			Structures of NF-kappaB p52 homodimer-DNA complexes rationalize binding mechanisms and transcription activation.,Pan W, Meshcheryakov VA, Li T, Wang Y, Ghosh G, Wang VY Elife. 2023 Feb 13;12:e86258. doi: 10.7554/eLife.86258. PMID:36779700<ref>PMID:36779700</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7cli" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[NF-kB\|NF-kB]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Z-~~disk~~]]		[[Category: Meshcheryakov VA]]
			[[Category: Wang VY-F]]

OCA at 08:57, 21 July 2021

2021-07-21T08:57:03Z

← Older revision		Revision as of 08:57, 21 July 2021
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7cli is ~~ON HOLD until Paper Publication~~		====
			<StructureSection load='7cli' size='340' side='right'caption='[[7cli]]' scene=''>
	~~Authors~~: ~~Meshcheryakov~~, V.A., ~~Wang~~, V.Y.-F.		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
	~~Description: Structure of NF-kB p52 homodimer bound to P-Selectin kB DNA fragment~~		</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=7cli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cli OCA], [https://pdbe.org/7cli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cli RCSB], [https://www.ebi.ac.uk/pdbsum/7cli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cli ProSAT]</span></td></tr>
	[[Category: ~~Unreleased~~ Structures]]		</table>
	[[Category: ~~Wang, V.Y.~~-~~F]]~~		__TOC__
	~~[[Category: Meshcheryakov, V.A~~]]		</StructureSection>
			[[Category: Large Structures]]
			[[Category: Z-disk]]

OCA at 09:16, 3 February 2021

2021-02-03T09:16:05Z

← Older revision		Revision as of 09:16, 3 February 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7cli is ON HOLD		The entry 7cli is ON HOLD until Paper Publication

	Authors: Meshcheryakov, V.A., Wang, V.Y.-F.		Authors: Meshcheryakov, V.A., Wang, V.Y.-F.

OCA: Protected "7cli" [edit=sysop:move=sysop]

2020-07-29T09:43:14Z

Protected "7cli" [edit=sysop:move=sysop]

← Older revision	Revision as of 09:43, 29 July 2020
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7cli is ON HOLD Authors: Meshcheryakov, V.A., Wang, V.Y.-F. Description: Structure of NF-kB p52 homodimer bound to P-Selectin kB DNA fragment [[Cat...

2020-07-29T09:43:13Z

New page: '''Unreleased structure''' The entry 7cli is ON HOLD Authors: Meshcheryakov, V.A., Wang, V.Y.-F. Description: Structure of NF-kB p52 homodimer bound to P-Selectin kB DNA fragment [[Cat...

New page

'''Unreleased structure'''

The entry 7cli is ON HOLD

Authors: Meshcheryakov, V.A., Wang, V.Y.-F.

Description: Structure of NF-kB p52 homodimer bound to P-Selectin kB DNA fragment
[[Category: Unreleased Structures]]
[[Category: Wang, V.Y.-F]]
[[Category: Meshcheryakov, V.A]]