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5jja

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Revision as of 07:52, 10 June 2020

Crystal structure of a PP2A B56gamma/BubR1 complex

Structural highlights

5jja is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	PPP2R5C, KIAA0044 (HUMAN), BUB1B, BUBR1, MAD3L, SSK1 (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[BUB1B_HUMAN] Mosaic variegated aneuploidy syndrome. Defects in BUB1B are associated with tumor formation. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. MVA1 is caused by biallelic mutations in the BUB1B gene.

Function

[2A5G_HUMAN] The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. The PP2A-PPP2R5C holoenzyme may specifically dephosphorylate and activate TP53 and play a role in DNA damage-induced inhibition of cell proliferation. PP2A-PPP2R5C may also regulate the ERK signaling pathway through ERK dephosphorylation.^[1] ^[2] [BUB1B_HUMAN] Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression.^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

Protein phosphatase 2A (PP2A) accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a catalytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kinetochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1. The PP2A-BubR1 interaction plays important roles in both spindle checkpoint silencing and stable microtubule-kinetochore attachment. Here we present the crystal structure of a PP2A B56-BubR1 complex, which demonstrates that a conserved BubR1 LxxIxE motif binds to the concave side of the B56 pseudo-HEAT repeats. The BubR1 motif binds to a groove formed between B56 HEAT repeats 3 and 4, which is quite distant from the B56 binding surface for PP2A catalytic C subunit and thus is unlikely to affect PP2A activity. In addition, the BubR1 binding site on B56 is far from the B56 binding site of shugoshin, another kinetochore PP2A-binding protein, and thus BubR1 and shugoshin can potentially interact with PP2A-B56 simultaneously. Our structural and biochemical analysis indicates that other proteins with the LxxIxE motif may also bind to the same PP2A B56 surface. Thus, our structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets.

Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization.,Wang J, Wang Z, Yu T, Yang H, Virshup DM, Kops GJ, Lee SH, Zhou W, Li X, Xu W, Rao Z Protein Cell. 2016 Jul;7(7):516-26. doi: 10.1007/s13238-016-0283-4. Epub 2016 Jun, 28. PMID:27350047^[9]

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

References

↑ Letourneux C, Rocher G, Porteu F. B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK. EMBO J. 2006 Feb 22;25(4):727-38. Epub 2006 Feb 2. PMID:16456541 doi:http://dx.doi.org/10.1038/sj.emboj.7600980
↑ Li HH, Cai X, Shouse GP, Piluso LG, Liu X. A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. EMBO J. 2007 Jan 24;26(2):402-11. PMID:17245430 doi:http://dx.doi.org/10.1038/sj.emboj.7601519
↑ Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ. Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. J Cell Biol. 1999 Sep 6;146(5):941-54. PMID:10477750
↑ Tang Z, Bharadwaj R, Li B, Yu H. Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. Dev Cell. 2001 Aug;1(2):227-37. PMID:11702782
↑ Shin HJ, Baek KH, Jeon AH, Park MT, Lee SJ, Kang CM, Lee HS, Yoo SH, Chung DH, Sung YC, McKeon F, Lee CW. Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of chromosomal instability. Cancer Cell. 2003 Dec;4(6):483-97. PMID:14706340
↑ 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
↑ Park SY, Kim S, Cho H, Kwon SH, Chae S, Kang D, Seong YS, Cho H. Depletion of BubR1 promotes premature centrosomal localization of cyclin B1 and accelerates mitotic entry. Cell Cycle. 2009 Jun 1;8(11):1754-64. Epub 2009 Jun 4. PMID:19411850
↑ Izumi H, Matsumoto Y, Ikeuchi T, Saya H, Kajii T, Matsuura S. BubR1 localizes to centrosomes and suppresses centrosome amplification via regulating Plk1 activity in interphase cells. Oncogene. 2009 Aug 6;28(31):2806-20. doi: 10.1038/onc.2009.141. Epub 2009 Jun 8. PMID:19503101 doi:http://dx.doi.org/10.1038/onc.2009.141
↑ Wang J, Wang Z, Yu T, Yang H, Virshup DM, Kops GJ, Lee SH, Zhou W, Li X, Xu W, Rao Z. Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization. Protein Cell. 2016 Jul;7(7):516-26. doi: 10.1007/s13238-016-0283-4. Epub 2016 Jun, 28. PMID:27350047 doi:http://dx.doi.org/10.1007/s13238-016-0283-4

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Crystal structure of a PP2A B56gamma/BubR1 complex==
-<StructureSection load='5jja' size='340' side='right' caption='[[5jja]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
+<StructureSection load='5jja' size='340' side='right'caption='[[5jja]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5jja]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JJA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JJA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5jja]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JJA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JJA FirstGlance]. <br>
-</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>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPP2R5C, KIAA0044 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BUB1B, BUBR1, MAD3L, SSK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5jja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jja OCA], [http://pdbe.org/5jja PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jja RCSB], [http://www.ebi.ac.uk/pdbsum/5jja PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jja ProSAT]</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://proteopedia.org/fgij/fg.htm?mol=5jja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jja OCA], [http://pdbe.org/5jja PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jja RCSB], [http://www.ebi.ac.uk/pdbsum/5jja PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jja ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5jja" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]]
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Rao, Z]]

5jja

From Proteopedia

Revision as of 07:52, 10 June 2020

Crystal structure of a PP2A B56gamma/BubR1 complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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