4r8q: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4r8q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3e7e 3e7e]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R8Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R8Q FirstGlance]. <br>
<table><tr><td colspan='2'>[[4r8q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3e7e 3e7e]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R8Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R8Q FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <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]] 2.31&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4r8q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8q OCA], [https://pdbe.org/4r8q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r8q RCSB], [https://www.ebi.ac.uk/pdbsum/4r8q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8q 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=4r8q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8q OCA], [https://pdbe.org/4r8q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r8q RCSB], [https://www.ebi.ac.uk/pdbsum/4r8q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8q ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/BUB1_HUMAN BUB1_HUMAN] Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Plays an important role in defining SGOL1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.<ref>PMID:10198256</ref> <ref>PMID:15020684</ref> <ref>PMID:15525512</ref> <ref>PMID:15723797</ref> <ref>PMID:16760428</ref> <ref>PMID:17158872</ref> <ref>PMID:19487456</ref>  
[https://www.uniprot.org/uniprot/BUB1_HUMAN BUB1_HUMAN] Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Plays an important role in defining SGOL1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.<ref>PMID:10198256</ref> <ref>PMID:15020684</ref> <ref>PMID:15525512</ref> <ref>PMID:15723797</ref> <ref>PMID:16760428</ref> <ref>PMID:17158872</ref> <ref>PMID:19487456</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In mitosis, the spindle checkpoint detects a single unattached kinetochore, inhibits the anaphase-promoting complex or cyclosome (APC/C), and prevents premature sister chromatid separation. The checkpoint kinase Bub1 contributes to checkpoint sensitivity through phosphorylating the APC/C activator, Cdc20, and inhibiting APC/C catalytically. We report here the crystal structure of the kinase domain of Bub1, revealing the requirement of an N-terminal extension for its kinase activity. Though the activation segment of Bub1 is ordered and has structural features indicative of active kinases, the C-terminal portion of this segment sterically restricts substrate access to the active site. Bub1 uses docking motifs, so-called KEN boxes, outside its kinase domain to recruit Cdc20, one of two known KEN box receptors. The KEN boxes of Bub1 are required for the spindle checkpoint in human cells. Therefore, its unusual active-site conformation and mode of substrate recruitment suggest that Bub1 has an exquisitely tuned specificity for Cdc20.
Structure and substrate recruitment of the human spindle checkpoint kinase Bub1.,Kang J, Yang M, Li B, Qi W, Zhang C, Shokat KM, Tomchick DR, Machius M, Yu H Mol Cell. 2008 Nov 7;32(3):394-405. PMID:18995837<ref>PMID:18995837</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4r8q" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==

Latest revision as of 15:51, 1 March 2024

Structure and substrate recruitment of the human spindle checkpoint kinase bub1Structure and substrate recruitment of the human spindle checkpoint kinase bub1

Structural highlights

4r8q is a 1 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 3e7e. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.31Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BUB1_HUMAN Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Plays an important role in defining SGOL1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.[1] [2] [3] [4] [5] [6] [7]

See Also

References

  1. ↑ Seeley TW, Wang L, Zhen JY. Phosphorylation of human MAD1 by the BUB1 kinase in vitro. Biochem Biophys Res Commun. 1999 Apr 13;257(2):589-95. PMID:10198256 doi:http://dx.doi.org/S0006-291X(99)90514-4
  2. ↑ Johnson VL, Scott MI, Holt SV, Hussein D, Taylor SS. Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression. J Cell Sci. 2004 Mar 15;117(Pt 8):1577-89. PMID:15020684 doi:http://dx.doi.org/10.1242/jcs.01006
  3. ↑ Tang Z, Shu H, Oncel D, Chen S, Yu H. Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint. Mol Cell. 2004 Nov 5;16(3):387-97. PMID:15525512 doi:http://dx.doi.org/10.1016/j.molcel.2004.09.031
  4. ↑ Kitajima TS, Hauf S, Ohsugi M, Yamamoto T, Watanabe Y. Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization. Curr Biol. 2005 Feb 22;15(4):353-9. PMID:15723797 doi:http://dx.doi.org/S0960982204010267
  5. ↑ Qi W, Tang Z, Yu H. Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is required for the kinetochore localization of Plk1. Mol Biol Cell. 2006 Aug;17(8):3705-16. Epub 2006 Jun 7. PMID:16760428 doi:http://dx.doi.org/10.1091/mbc.E06-03-0240
  6. ↑ Qi W, Yu H. KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome. J Biol Chem. 2007 Feb 9;282(6):3672-9. Epub 2006 Dec 11. PMID:17158872 doi:http://dx.doi.org/10.1074/jbc.M609376200
  7. ↑ Klebig C, Korinth D, Meraldi P. Bub1 regulates chromosome segregation in a kinetochore-independent manner. J Cell Biol. 2009 Jun 1;185(5):841-58. doi: 10.1083/jcb.200902128. PMID:19487456 doi:http://dx.doi.org/10.1083/jcb.200902128

4r8q, resolution 2.31Å

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