5tvb - Revision history

OCA at 15:43, 6 March 2024

OCA — Wed, 06 Mar 2024 15:43:33 GMT

←Older revision		Revision as of 15:43, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='5tvb' size='340' side='right'caption='[[5tvb]], [[Resolution\|resolution]] 2.75Å' scene=''>		<StructureSection load='5tvb' size='340' side='right'caption='[[5tvb]], [[Resolution\|resolution]] 2.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tvb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TVB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5TVB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tvb]] is a 2 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=5TVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TVB FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non~~-~~Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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]] 2.75Å</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=5tvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tvb OCA], [~~http~~://pdbe.org/5tvb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5tvb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5tvb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5tvb ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=5tvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tvb OCA], [https://pdbe.org/5tvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tvb RCSB], [https://www.ebi.ac.uk/pdbsum/5tvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tvb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/TPR_HUMAN TPR_HUMAN]] Papillary or follicular thyroid carcinoma. A chromosomal aberration involving TPR has been found in papillary thyroid carcinomas (PTCs). Intrachromosomal rearrangement that links the 5'-end of the TPR gene to the protein kinase domain of NTRK1 forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the carboxy terminus of the NTRK1 protein.<ref>PMID:1532241</ref> Involved in tumorigenic rearrangements with the MET.<ref>PMID:2300559</ref>	+	[https://www.uniprot.org/uniprot/TPR_HUMAN TPR_HUMAN] Papillary or follicular thyroid carcinoma. A chromosomal aberration involving TPR has been found in papillary thyroid carcinomas (PTCs). Intrachromosomal rearrangement that links the 5'-end of the TPR gene to the protein kinase domain of NTRK1 forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the carboxy terminus of the NTRK1 protein.<ref>PMID:1532241</ref> Involved in tumorigenic rearrangements with the MET.<ref>PMID:2300559</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TPR_HUMAN TPR_HUMAN]] Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:22253824 and PubMed:11952838). Plays also a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases.<ref>PMID:11952838</ref> <ref>PMID:15654337</ref> <ref>PMID:17897941</ref> <ref>PMID:18794356</ref> <ref>PMID:18981471</ref> <ref>PMID:19273613</ref> <ref>PMID:20133940</ref> <ref>PMID:20407419</ref> <ref>PMID:21613532</ref> <ref>PMID:22253824</ref> <ref>PMID:9864356</ref>	+	[https://www.uniprot.org/uniprot/TPR_HUMAN TPR_HUMAN] Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:22253824 and PubMed:11952838). Plays also a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases.<ref>PMID:11952838</ref> <ref>PMID:15654337</ref> <ref>PMID:17897941</ref> <ref>PMID:18794356</ref> <ref>PMID:18981471</ref> <ref>PMID:19273613</ref> <ref>PMID:20133940</ref> <ref>PMID:20407419</ref> <ref>PMID:21613532</ref> <ref>PMID:22253824</ref> <ref>PMID:9864356</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The nuclear pore complex subunit TPR is found in at least five different oncogenic fusion kinases, including TPR-MET, yet how TPR fusions promote activation of kinases and their oncogenic activities remains poorly understood. Here we report the crystal structure of TPR(2-142), the MET fusion partner of oncogenic TPR-MET. TPR(2-142) contains a continuous 124-residue alpha helix that forms an antiparallel tetramer from two leucine zipper-containing parallel coiled coils. Remarkably, single mutations cause strikingly different conformations of the coiled coil, indicating its highly dynamic nature. We further show that fusion of TPR(2-142) to the MET intracellular domain strongly and selectively stabilizes the alphaG helix of the MET kinase domain, and mutations of only the TPR leucine zipper residues at the junction to MET, but not other leucine zipper residues, abolish kinase activation. Together, these results provide critical insight into the TPR structure and its ability to induce dimerization and activation of fusion kinases.	+
-		+
-	Structural Basis of TPR-Mediated Oligomerization and Activation of Oncogenic Fusion Kinases.,Pal K, Bandyopadhyay A, Zhou XE, Xu Q, Marciano DP, Brunzelle JS, Yerrum S, Griffin PR, Vande Woude G, Melcher K, Xu HE Structure. 2017 Jun 6;25(6):867-877.e3. doi: 10.1016/j.str.2017.04.015. Epub 2017, May 18. PMID:28528776<ref>PMID:28528776</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5tvb" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Melcher, K]]	+	[[Category: Melcher K]]
-	[[Category: Pal, K]]	+	[[Category: Pal K]]
-	[[Category: Xu~~, H E~~]]	+	[[Category: Xu HE]]
-	[[Category: Xu, Q]]	+	[[Category: Xu Q]]
-	[[Category: Zhou~~, X E]]~~	+	[[Category: Zhou XE]]
-	~~[[Category: Oncogenic fusion kinase]]~~	+
-	~~[[Category: Receptor tyrosine kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 12:20, 23 September 2020

OCA — Wed, 23 Sep 2020 12:20:43 GMT

←Older revision		Revision as of 12:20, 23 September 2020
Line 1:		Line 1:

	==Structure of the TPR oligomerization domain==		==Structure of the TPR oligomerization domain==
-	<StructureSection load='5tvb' size='340' side='right' caption='[[5tvb]], [[Resolution\|resolution]] 2.75Å' scene=''>	+	<StructureSection load='5tvb' size='340' side='right'caption='[[5tvb]], [[Resolution\|resolution]] 2.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tvb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TVB OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5TVB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tvb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TVB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5TVB FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=5tvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tvb OCA], [http://pdbe.org/5tvb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tvb RCSB], [http://www.ebi.ac.uk/pdbsum/5tvb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tvb 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=5tvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tvb OCA], [http://pdbe.org/5tvb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tvb RCSB], [http://www.ebi.ac.uk/pdbsum/5tvb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tvb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5tvb" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5tvb" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nucleoprotein 3D structures\|Nucleoprotein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Melcher, K]]		[[Category: Melcher, K]]
	[[Category: Pal, K]]		[[Category: Pal, K]]

OCA at 04:41, 21 September 2017

OCA — Thu, 21 Sep 2017 04:41:33 GMT

←Older revision		Revision as of 04:41, 21 September 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5tvb is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of the TPR oligomerization domain==
		+	<StructureSection load='5tvb' size='340' side='right' caption='[[5tvb]], [[Resolution\|resolution]] 2.75Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5tvb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TVB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TVB FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=5tvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tvb OCA], [http://pdbe.org/5tvb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tvb RCSB], [http://www.ebi.ac.uk/pdbsum/5tvb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tvb ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/TPR_HUMAN TPR_HUMAN]] Papillary or follicular thyroid carcinoma. A chromosomal aberration involving TPR has been found in papillary thyroid carcinomas (PTCs). Intrachromosomal rearrangement that links the 5'-end of the TPR gene to the protein kinase domain of NTRK1 forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the carboxy terminus of the NTRK1 protein.<ref>PMID:1532241</ref> Involved in tumorigenic rearrangements with the MET.<ref>PMID:2300559</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TPR_HUMAN TPR_HUMAN]] Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:22253824 and PubMed:11952838). Plays also a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases.<ref>PMID:11952838</ref> <ref>PMID:15654337</ref> <ref>PMID:17897941</ref> <ref>PMID:18794356</ref> <ref>PMID:18981471</ref> <ref>PMID:19273613</ref> <ref>PMID:20133940</ref> <ref>PMID:20407419</ref> <ref>PMID:21613532</ref> <ref>PMID:22253824</ref> <ref>PMID:9864356</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The nuclear pore complex subunit TPR is found in at least five different oncogenic fusion kinases, including TPR-MET, yet how TPR fusions promote activation of kinases and their oncogenic activities remains poorly understood. Here we report the crystal structure of TPR(2-142), the MET fusion partner of oncogenic TPR-MET. TPR(2-142) contains a continuous 124-residue alpha helix that forms an antiparallel tetramer from two leucine zipper-containing parallel coiled coils. Remarkably, single mutations cause strikingly different conformations of the coiled coil, indicating its highly dynamic nature. We further show that fusion of TPR(2-142) to the MET intracellular domain strongly and selectively stabilizes the alphaG helix of the MET kinase domain, and mutations of only the TPR leucine zipper residues at the junction to MET, but not other leucine zipper residues, abolish kinase activation. Together, these results provide critical insight into the TPR structure and its ability to induce dimerization and activation of fusion kinases.

-	~~Authors: Pal~~, K., Xu, Q., ~~Zhou~~, ~~X.E.~~, ~~Melcher~~, K., Xu~~, H~~.E.	+	Structural Basis of TPR-Mediated Oligomerization and Activation of Oncogenic Fusion Kinases.,Pal K, Bandyopadhyay A, Zhou XE, Xu Q, Marciano DP, Brunzelle JS, Yerrum S, Griffin PR, Vande Woude G, Melcher K, Xu HE Structure. 2017 Jun 6;25(6):867-877.e3. doi: 10.1016/j.str.2017.04.015. Epub 2017, May 18. PMID:28528776<ref>PMID:28528776</ref>

-	~~Description: Structure~~ of the ~~TPR oligomerization domain~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Zhou, X.E]]~~	+	<div class="pdbe-citations 5tvb" style="background-color:#fffaf0;"></div>
-	~~[[Category: Xu, H.E]]~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Melcher, K]]		[[Category: Melcher, K]]
-	[[Category: Xu, Q]]
	[[Category: Pal, K]]		[[Category: Pal, K]]
		+	[[Category: Xu, H E]]
		+	[[Category: Xu, Q]]
		+	[[Category: Zhou, X E]]
		+	[[Category: Oncogenic fusion kinase]]
		+	[[Category: Receptor tyrosine kinase]]
		+	[[Category: Transferase]]

OCA: Protected "5tvb" [edit=sysop:move=sysop]

OCA — Fri, 09 Dec 2016 17:55:48 GMT

Protected "5tvb" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:55, 9 December 2016

OCA: New page: '''Unreleased structure''' The entry 5tvb is ON HOLD until Paper Publication Authors: Pal, K., Xu, Q., Zhou, X.E., Melcher, K., Xu, H.E. Description: Structure of the TPR oligomerizati...

OCA — Fri, 09 Dec 2016 17:55:47 GMT

New page: '''Unreleased structure''' The entry 5tvb is ON HOLD until Paper Publication Authors: Pal, K., Xu, Q., Zhou, X.E., Melcher, K., Xu, H.E. Description: Structure of the TPR oligomerizati...

New page

'''Unreleased structure'''

The entry 5tvb is ON HOLD until Paper Publication

Authors: Pal, K., Xu, Q., Zhou, X.E., Melcher, K., Xu, H.E.

Description: Structure of the TPR oligomerization domain
[[Category: Unreleased Structures]]
[[Category: Zhou, X.E]]
[[Category: Xu, H.E]]
[[Category: Melcher, K]]
[[Category: Xu, Q]]
[[Category: Pal, K]]