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5xqz

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Revision as of 06:57, 14 October 2020

Structure of the MOB1-NDR2 complex

Structural highlights

5xqz is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] [ST38L_HUMAN] Involved in the regulation of structural processes in differentiating and mature neuronal cells.^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bichsel SJ, Tamaskovic R, Stegert MR, Hemmings BA. Mechanism of activation of NDR (nuclear Dbf2-related) protein kinase by the hMOB1 protein. J Biol Chem. 2004 Aug 20;279(34):35228-35. Epub 2004 Jun 14. PMID:15197186 doi:10.1074/jbc.M404542200
↑ Hirabayashi S, Nakagawa K, Sumita K, Hidaka S, Kawai T, Ikeda M, Kawata A, Ohno K, Hata Y. Threonine 74 of MOB1 is a putative key phosphorylation site by MST2 to form the scaffold to activate nuclear Dbf2-related kinase 1. Oncogene. 2008 Jul 17;27(31):4281-92. doi: 10.1038/onc.2008.66. Epub 2008 Mar 24. PMID:18362890 doi:10.1038/onc.2008.66
↑ Chow A, Hao Y, Yang X. Molecular characterization of human homologs of yeast MOB1. Int J Cancer. 2010 May 1;126(9):2079-89. doi: 10.1002/ijc.24878. PMID:19739119 doi:10.1002/ijc.24878
↑ Stegert MR, Tamaskovic R, Bichsel SJ, Hergovich A, Hemmings BA. Regulation of NDR2 protein kinase by multi-site phosphorylation and the S100B calcium-binding protein. J Biol Chem. 2004 May 28;279(22):23806-12. Epub 2004 Mar 22. PMID:15037617 doi:http://dx.doi.org/10.1074/jbc.M402472200
↑ Devroe E, Erdjument-Bromage H, Tempst P, Silver PA. Human Mob proteins regulate the NDR1 and NDR2 serine-threonine kinases. J Biol Chem. 2004 Jun 4;279(23):24444-51. Epub 2004 Apr 2. PMID:15067004 doi:http://dx.doi.org/10.1074/jbc.M401999200
↑ 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. Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control. Nat Commun. 2017 Sep 25;8(1):695. doi: 10.1038/s41467-017-00795-y. PMID:28947795 doi:http://dx.doi.org/10.1038/s41467-017-00795-y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5xqz"

Categories: Large Structures | Non-specific serine/threonine protein kinase | Lin, K | Wu, G | Signaling protein-transferase complex

@@ Line 1: / Line 1: @@
 ==Structure of the MOB1-NDR2 complex==
-<StructureSection load='5xqz' size='340' side='right' caption='[[5xqz]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='5xqz' size='340' side='right'caption='[[5xqz]], [[Resolution|resolution]] 2.10&Aring;' 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>
+<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='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>
 == Function ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Lin, K]]
 [[Category: Wu, G]]
 [[Category: Signaling protein-transferase complex]]

5xqz

From Proteopedia

Revision as of 06:57, 14 October 2020

Structure of the MOB1-NDR2 complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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