4bl0: Difference between revisions

Latest revision as of 08:16, 9 October 2024

Crystal structure of yeast Bub3-Bub1 bound to phospho-Spc105

Structural highlights

4bl0 is a 6 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.95Å
Ligands:	MG, TPO
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BUB1_YEAST Involved in cell cycle checkpoint enforcement. The formation of a MAD1-BUB1-BUB3 complex seems to be required for the spindle checkpoint mechanism. Catalyzes the phosphorylation of BUB3 and its autophosphorylation. Associates with centromere (CEN) DNA via interaction with SKP1. The association with SKP1 is required for the mitotic delay induced by kinetochore tension defects, but not for the arrest induced by spindle depolymerization or kinetochore assembly defects.^[1]

Publication Abstract from PubMed

Regulation of macromolecular interactions by phosphorylation is crucial in signaling networks. In the spindle assembly checkpoint (SAC), which enables errorless chromosome segregation, phosphorylation promotes recruitment of SAC proteins to tensionless kinetochores. The SAC kinase Mps1 phosphorylates multiple Met-Glu-Leu-Thr (MELT) motifs on the kinetochore subunit Spc105/Knl1. The phosphorylated MELT motifs (MELT(P)) then promote recruitment of downstream signaling components. How MELT(P) motifs are recognized is unclear. In this study, we report that Bub3, a 7-bladed beta-propeller, is the MELT(P) reader. It contains an exceptionally well-conserved interface that docks the MELT(P) sequence on the side of the beta-propeller in a previously unknown binding mode. Mutations targeting the Bub3 interface prevent kinetochore recruitment of the SAC kinase Bub1. Crucially, they also cause a checkpoint defect, showing that recognition of phosphorylated targets by Bub3 is required for checkpoint signaling. Our data provide the first detailed mechanistic insight into how phosphorylation promotes recruitment of checkpoint proteins to kinetochores. DOI:https://dx.doi.org/10.7554/eLife.01030.001.

Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling.,Primorac I, Weir JR, Chiroli E, Gross F, Hoffmann I, van Gerwen S, Ciliberto A, Musacchio A Elife. 2013 Sep 24;2:e01030. doi: 10.7554/eLife.01030. PMID:24066227^[2]

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

References

↑ Kitagawa K, Abdulle R, Bansal PK, Cagney G, Fields S, Hieter P. Requirement of Skp1-Bub1 interaction for kinetochore-mediated activation of the spindle checkpoint. Mol Cell. 2003 May;11(5):1201-13. PMID:12769845
↑ Primorac I, Weir JR, Chiroli E, Gross F, Hoffmann I, van Gerwen S, Ciliberto A, Musacchio A. Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling. Elife. 2013 Sep 24;2:e01030. doi: 10.7554/eLife.01030. PMID:24066227 doi:https://dx.doi.org/10.7554/eLife.01030

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Kitagawa K, Abdulle R, Bansal PK, Cagney G, Fields S, Hieter P. Requirement of Skp1-Bub1 interaction for kinetochore-mediated activation of the spindle checkpoint. Mol Cell. 2003 May;11(5):1201-13. PMID:12769845

[2] Primorac I, Weir JR, Chiroli E, Gross F, Hoffmann I, van Gerwen S, Ciliberto A, Musacchio A. Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling. Elife. 2013 Sep 24;2:e01030. doi: 10.7554/eLife.01030. PMID:24066227 doi:https://dx.doi.org/10.7554/eLife.01030

[1]

[2]

@@ Line 3: / Line 3: @@
 <StructureSection load='4bl0' size='340' side='right'caption='[[4bl0]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4bl0]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BL0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BL0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4bl0]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BL0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BL0 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.95&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://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=4bl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bl0 OCA], [https://pdbe.org/4bl0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bl0 RCSB], [https://www.ebi.ac.uk/pdbsum/4bl0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bl0 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/BUB3_YEAST BUB3_YEAST]] Required for cell cycle arrest in response to loss of microtubule function. Component of the spindle assembly checkpoint which is a feedback control that prevents cells with incompletely assembled spindles from leaving mitosis. Component of the mitotic checkpoint complex (MCC) which inhibits the ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) by preventing its activation by CDC20. The formation of a MAD1-BUB1-BUB3 complex seems to be required for the spindle checkpoint mechanism.<ref>PMID:15879521</ref>  [[https://www.uniprot.org/uniprot/SP105_YEAST SP105_YEAST]] Forms a kinetochore complex with SPC105 which is required for kinetochore binding by a discrete subset of kMAPs (BIM1, BIK1 and SLK19) and motors (CIN8, KAR3). Involved in kinetochore-microtubule binding and the spindle assembly checkpoint.<ref>PMID:19893618</ref>  [[https://www.uniprot.org/uniprot/BUB1_YEAST BUB1_YEAST]] Involved in cell cycle checkpoint enforcement. The formation of a MAD1-BUB1-BUB3 complex seems to be required for the spindle checkpoint mechanism. Catalyzes the phosphorylation of BUB3 and its autophosphorylation. Associates with centromere (CEN) DNA via interaction with SKP1. The association with SKP1 is required for the mitotic delay induced by kinetochore tension defects, but not for the arrest induced by spindle depolymerization or kinetochore assembly defects.<ref>PMID:12769845</ref>
+[https://www.uniprot.org/uniprot/BUB1_YEAST BUB1_YEAST] Involved in cell cycle checkpoint enforcement. The formation of a MAD1-BUB1-BUB3 complex seems to be required for the spindle checkpoint mechanism. Catalyzes the phosphorylation of BUB3 and its autophosphorylation. Associates with centromere (CEN) DNA via interaction with SKP1. The association with SKP1 is required for the mitotic delay induced by kinetochore tension defects, but not for the arrest induced by spindle depolymerization or kinetochore assembly defects.<ref>PMID:12769845</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Atcc 18824]]
 [[Category: Large Structures]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Saccharomyces cerevisiae]]
-[[Category: Musacchio, A]]
+[[Category: Musacchio A]]
-[[Category: Primorac, I]]
+[[Category: Primorac I]]
-[[Category: Weir, J R]]
+[[Category: Weir JR]]
-[[Category: Aneuploidy]]
-[[Category: Blinkin]]
-[[Category: Bubr1]]
-[[Category: Casc5]]
-[[Category: Cell cycle]]
-[[Category: Cell division]]
-[[Category: Gle2]]
-[[Category: Gleb]]
-[[Category: Kinetochore]]
-[[Category: Knl1]]
-[[Category: Mad1]]
-[[Category: Mad2]]
-[[Category: Mad3]]
-[[Category: Mitosis]]
-[[Category: Rae1]]
-[[Category: Spc7]]
-[[Category: Spindle assembly checkpoint]]

4bl0: Difference between revisions

Latest revision as of 08:16, 9 October 2024

Crystal structure of yeast Bub3-Bub1 bound to phospho-Spc105

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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