5xqz - Revision history

OCA at 10:19, 27 March 2024

OCA — Wed, 27 Mar 2024 10:19:48 GMT

←Older revision		Revision as of 10:19, 27 March 2024
Line 3:		Line 3:
	<StructureSection load='5xqz' size='340' side='right'caption='[[5xqz]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='5xqz' size='340' side='right'caption='[[5xqz]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xqz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XQZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5XQZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xqz]] 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=5XQZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XQZ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>~~, ~~<scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.1Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks~~'>~~[http:~~/~~/en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase]~~, ~~with EC number [http~~:~~//www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1]~~ </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5xqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xqz OCA], [~~http~~://pdbe.org/5xqz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5xqz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5xqz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5xqz 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=5xqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xqz OCA], [https://pdbe.org/5xqz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xqz RCSB], [https://www.ebi.ac.uk/pdbsum/5xqz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xqz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MOB1A_HUMAN MOB1A_HUMAN]] Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38 and STK38L. Acts cooperatively with STK3/MST2 to activate STK38.<ref>PMID:15197186</ref> <ref>PMID:18362890</ref> <ref>PMID:19739119</ref> [[http://www.uniprot.org/uniprot/ST38L_HUMAN ST38L_HUMAN]] Involved in the regulation of structural processes in differentiating and mature neuronal cells.<ref>PMID:15037617</ref> <ref>PMID:15067004</ref>	+	[https://www.uniprot.org/uniprot/MOB1A_HUMAN MOB1A_HUMAN] Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38 and STK38L. Acts cooperatively with STK3/MST2 to activate STK38.<ref>PMID:15197186</ref> <ref>PMID:18362890</ref> <ref>PMID:19739119</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1's differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction. By studying these variants in human cancer cells and Drosophila, we uncovered that MOB1/Warts binding is essential for tumor suppression, tissue growth control, and development, while stable MOB1/Hippo binding is dispensable and MOB1/Trc binding alone is insufficient. Collectively, we decrypt molecularly, cell biologically, and genetically the importance of the diverse interactions of Hippo core kinases with the pivotal MOB1 signal transducer.The Hippo tumor suppressor pathway is essential for development and tissue growth control. Here the authors employ a multi-disciplinary approach to characterize the interactions of the three Hippo kinases with the signaling adaptor MOB1 and show how they differently affect development, tissue growth and tumor suppression.	+
-		+
-	Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control.,Kulaberoglu Y, Lin K, Holder M, Gai Z, Gomez M, Assefa Shifa B, Mavis M, Hoa L, Sharif AAD, Lujan C, Smith ESJ, Bjedov I, Tapon N, Wu G, Hergovich A Nat Commun. 2017 Sep 25;8(1):695. doi: 10.1038/s41467-017-00795-y. PMID:28947795<ref>PMID:28947795</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5xqz" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Lin K]]
-	[[Category: Lin, K]]	+	[[Category: Wu G]]
-	[[Category: Wu, G]]	+
-	~~[[Category: Signaling protein-transferase complex~~]]	+

OCA at 06:57, 14 October 2020

OCA — Wed, 14 Oct 2020 06:57:17 GMT

←Older revision		Revision as of 06:57, 14 October 2020
Line 1:		Line 1:

	==Structure of the MOB1-NDR2 complex==		==Structure of the MOB1-NDR2 complex==
-	<StructureSection load='5xqz' size='340' side='right' caption='[[5xqz]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='5xqz' size='340' side='right'caption='[[5xqz]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xqz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XQZ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5XQZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xqz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XQZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XQZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=5xqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xqz OCA], [http://pdbe.org/5xqz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xqz RCSB], [http://www.ebi.ac.uk/pdbsum/5xqz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xqz 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=5xqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xqz OCA], [http://pdbe.org/5xqz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xqz RCSB], [http://www.ebi.ac.uk/pdbsum/5xqz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xqz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Lin, K]]		[[Category: Lin, K]]
	[[Category: Wu, G]]		[[Category: Wu, G]]
	[[Category: Signaling protein-transferase complex]]		[[Category: Signaling protein-transferase complex]]

OCA at 07:17, 29 August 2018

OCA — Wed, 29 Aug 2018 07:17:51 GMT

←Older revision		Revision as of 07:17, 29 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5xqz is ~~ON HOLD~~	+	==Structure of the MOB1-NDR2 complex==
		+	<StructureSection load='5xqz' size='340' side='right' caption='[[5xqz]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5xqz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XQZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XQZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=5xqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xqz OCA], [http://pdbe.org/5xqz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xqz RCSB], [http://www.ebi.ac.uk/pdbsum/5xqz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xqz ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MOB1A_HUMAN MOB1A_HUMAN]] Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38 and STK38L. Acts cooperatively with STK3/MST2 to activate STK38.<ref>PMID:15197186</ref> <ref>PMID:18362890</ref> <ref>PMID:19739119</ref> [[http://www.uniprot.org/uniprot/ST38L_HUMAN ST38L_HUMAN]] Involved in the regulation of structural processes in differentiating and mature neuronal cells.<ref>PMID:15037617</ref> <ref>PMID:15067004</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1's differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction. By studying these variants in human cancer cells and Drosophila, we uncovered that MOB1/Warts binding is essential for tumor suppression, tissue growth control, and development, while stable MOB1/Hippo binding is dispensable and MOB1/Trc binding alone is insufficient. Collectively, we decrypt molecularly, cell biologically, and genetically the importance of the diverse interactions of Hippo core kinases with the pivotal MOB1 signal transducer.The Hippo tumor suppressor pathway is essential for development and tissue growth control. Here the authors employ a multi-disciplinary approach to characterize the interactions of the three Hippo kinases with the signaling adaptor MOB1 and show how they differently affect development, tissue growth and tumor suppression.

-	~~Authors: Wu, G~~., ~~Lin~~, K.	+	Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control.,Kulaberoglu Y, Lin K, Holder M, Gai Z, Gomez M, Assefa Shifa B, Mavis M, Hoa L, Sharif AAD, Lujan C, Smith ESJ, Bjedov I, Tapon N, Wu G, Hergovich A Nat Commun. 2017 Sep 25;8(1):695. doi: 10.1038/s41467-017-00795-y. PMID:28947795<ref>PMID:28947795</ref>

-	~~Description: Structure~~ of the ~~MOB1-NDR2 complex~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Wu, G~~]]	+	<div class="pdbe-citations 5xqz" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Lin, K]]		[[Category: Lin, K]]
		+	[[Category: Wu, G]]
		+	[[Category: Signaling protein-transferase complex]]

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

OCA — Wed, 27 Sep 2017 15:41:54 GMT

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

←Older revision

Revision as of 15:41, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5xqz is ON HOLD Authors: Wu, G., Lin, K. Description: Structure of the MOB1-NDR2 complex Category: Unreleased Structures Category: Wu, G [[...

OCA — Wed, 27 Sep 2017 15:41:53 GMT

New page: '''Unreleased structure''' The entry 5xqz is ON HOLD Authors: Wu, G., Lin, K. Description: Structure of the MOB1-NDR2 complex Category: Unreleased Structures Category: Wu, G [[...

New page

'''Unreleased structure'''

The entry 5xqz is ON HOLD

Authors: Wu, G., Lin, K.

Description: Structure of the MOB1-NDR2 complex
[[Category: Unreleased Structures]]
[[Category: Wu, G]]
[[Category: Lin, K]]