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| | <StructureSection load='5ncn' size='340' side='right'caption='[[5ncn]], [[Resolution|resolution]] 3.50Å' scene=''> | | <StructureSection load='5ncn' size='340' side='right'caption='[[5ncn]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ncn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NCN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NCN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ncn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NCN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 3.501Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MOB1, YIL106W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), DBF2, YGR092W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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'>[https://proteopedia.org/fgij/fg.htm?mol=5ncn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ncn OCA], [https://pdbe.org/5ncn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ncn RCSB], [https://www.ebi.ac.uk/pdbsum/5ncn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ncn 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=5ncn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ncn OCA], [http://pdbe.org/5ncn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ncn RCSB], [http://www.ebi.ac.uk/pdbsum/5ncn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ncn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MOB1_YEAST MOB1_YEAST]] Functions as an activator subunit for the DBF2 protein kinase. Binds to DBF2, which is required for the phosphorylation and activation of DBF2 by the upstream kinase CDC15 in late anaphase. DBF2-MOB1 is part of the mitotic exit network (MEN) signaling cascade, which regulates release from the nucleus and activity of phosphatase CDC14. Required for inactivation of mitotic cyclin-dependent kinase for exit from mitosis, cytokinesis and G1 gene transcription.<ref>PMID:11564880</ref> <ref>PMID:11404483</ref> <ref>PMID:16176976</ref> [[http://www.uniprot.org/uniprot/DBF2_YEAST DBF2_YEAST]] Ser/Thr-protein kinase involved in the mitotic exit network (MEN) and required after the metaphase to anaphase cell cycle transition. Phosphorylates CHS2 to regulate its dynamics and chitin synthesis at the division site during cytokinesis. Coordinates septin and actomyosin ring (AMR) functions during cytokinesis through the phosphorylation of HOF1. In complex with MOB1, phosphorylates CDC14 at sites adjacent to its nuclear localization sequence, thereby retaining CDC14 in the cytoplasm. Binds also to SWI5 and CLB2 mRNAs cotranscriptionally to regulate their decay. In the nucleus, the DBF2-MOB1 complex regulates passenger protein localization during anaphase. Mediates sorbic acid stress tolerance through promoting vacuolar H(+)-ATPase function, probably through phosphorylation of VMA1 and VMA2 subunits.<ref>PMID:10228157</ref> <ref>PMID:10984431</ref> <ref>PMID:11378390</ref> <ref>PMID:11404483</ref> <ref>PMID:11598184</ref> <ref>PMID:12832486</ref> <ref>PMID:14551257</ref> <ref>PMID:16176976</ref> <ref>PMID:16242037</ref> <ref>PMID:18048916</ref> <ref>PMID:19221193</ref> <ref>PMID:20123997</ref> <ref>PMID:20442249</ref> <ref>PMID:22196726</ref> <ref>PMID:22573892</ref> <ref>PMID:23447700</ref> <ref>PMID:8131744</ref> <ref>PMID:9528782</ref> <ref>PMID:9613578</ref> | + | [https://www.uniprot.org/uniprot/MOB1_YEAST MOB1_YEAST] Functions as an activator subunit for the DBF2 protein kinase. Binds to DBF2, which is required for the phosphorylation and activation of DBF2 by the upstream kinase CDC15 in late anaphase. DBF2-MOB1 is part of the mitotic exit network (MEN) signaling cascade, which regulates release from the nucleus and activity of phosphatase CDC14. Required for inactivation of mitotic cyclin-dependent kinase for exit from mitosis, cytokinesis and G1 gene transcription.<ref>PMID:11564880</ref> <ref>PMID:11404483</ref> <ref>PMID:16176976</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Gogl, G]] | + | [[Category: Gogl G]] |
| - | [[Category: Parker, B]] | + | [[Category: Parker B]] |
| - | [[Category: Remenyi, A]] | + | [[Category: Remenyi A]] |
| - | [[Category: Weiss, E]] | + | [[Category: Weiss E]] |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
MOB1_YEAST Functions as an activator subunit for the DBF2 protein kinase. Binds to DBF2, which is required for the phosphorylation and activation of DBF2 by the upstream kinase CDC15 in late anaphase. DBF2-MOB1 is part of the mitotic exit network (MEN) signaling cascade, which regulates release from the nucleus and activity of phosphatase CDC14. Required for inactivation of mitotic cyclin-dependent kinase for exit from mitosis, cytokinesis and G1 gene transcription.[1] [2] [3]
Publication Abstract from PubMed
Ndr/Lats kinases bind Mob coactivator proteins to form complexes that are essential and evolutionarily conserved components of "Hippo" signaling pathways, which control cell proliferation and morphogenesis in eukaryotes. All Ndr/Lats kinases have a characteristic N-terminal regulatory (NTR) region that binds a specific Mob cofactor: Lats kinases associate with Mob1 proteins, and Ndr kinases associate with Mob2 proteins. To better understand the significance of the association of Mob protein with Ndr/Lats kinases and selective binding of Ndr and Lats to distinct Mob cofactors, we determined crystal structures of Saccharomyces cerevisiae Cbk1(NTR)-Mob2 and Dbf2(NTR)-Mob1 and experimentally assessed determinants of Mob cofactor binding and specificity. This allowed a significant improvement in the previously determined structure of Cbk1 kinase bound to Mob2, presently the only crystallographic model of a full length Ndr/Lats kinase complexed with a Mob cofactor. Our analysis indicates that the Ndr/Lats(NTR)-Mob interface provides a distinctive kinase regulation mechanism, in which the Mob cofactor organizes the Ndr/Lats NTR to interact with the AGC kinase C-terminal hydrophobic motif (HM), which is involved in allosteric regulation. The Mob-organized NTR appears to mediate association of the HM with an allosteric site on the N-terminal kinase lobe. We also found that Cbk1 and Dbf2 associated specifically with Mob2 and Mob1, respectively. Alteration of residues in the Cbk1 NTR allows association of the noncognate Mob cofactor, indicating that cofactor specificity is restricted by discrete sites rather than being broadly distributed. Overall, our analysis provides a new picture of the functional role of Mob association and indicates that the Ndr/Lats(NTR)-Mob interface is largely a common structural platform that mediates kinase-cofactor binding.
Ndr/Lats Kinases Bind Specific Mob-Family Coactivators through a Conserved and Modular Interface.,Parker BW, Gogl G, Balint M, Hetenyi C, Remenyi A, Weiss EL Biochemistry. 2020 May 5;59(17):1688-1700. doi: 10.1021/acs.biochem.9b01096. Epub, 2020 Apr 17. PMID:32250593[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Luca FC, Mody M, Kurischko C, Roof DM, Giddings TH, Winey M. Saccharomyces cerevisiae Mob1p is required for cytokinesis and mitotic exit. Mol Cell Biol. 2001 Oct;21(20):6972-83. PMID:11564880 doi:http://dx.doi.org/10.1128/MCB.21.20.6972-6983.2001
- ↑ Mah AS, Jang J, Deshaies RJ. Protein kinase Cdc15 activates the Dbf2-Mob1 kinase complex. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7325-30. Epub 2001 Jun 12. PMID:11404483 doi:http://dx.doi.org/10.1073/pnas.141098998
- ↑ Stoepel J, Ottey MA, Kurischko C, Hieter P, Luca FC. The mitotic exit network Mob1p-Dbf2p kinase complex localizes to the nucleus and regulates passenger protein localization. Mol Biol Cell. 2005 Dec;16(12):5465-79. Epub 2005 Sep 21. PMID:16176976 doi:http://dx.doi.org/E05-04-0337
- ↑ Parker BW, Gogl G, Balint M, Hetenyi C, Remenyi A, Weiss EL. Ndr/Lats Kinases Bind Specific Mob-Family Coactivators through a Conserved and Modular Interface. Biochemistry. 2020 May 5;59(17):1688-1700. doi: 10.1021/acs.biochem.9b01096. Epub, 2020 Apr 17. PMID:32250593 doi:http://dx.doi.org/10.1021/acs.biochem.9b01096
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