4i5n

From Proteopedia

(Difference between revisions)

Current revision

Structural mechanism of trimeric PP2A holoenzyme involving PR70: insight for Cdc6 dephosphorylation

Structural highlights

4i5n is a 8 chain structure with sequence from Homo sapiens and Microcystis aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:	, , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CDC6_HUMAN Defects in CDC6 are the cause of Meier-Gorlin syndrome type 5 (MGORS5) [MIM:613805. MGORS5 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.^[1]

Function

P2R3B_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.CDC6_HUMAN Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.

Publication Abstract from PubMed

The B/PR72 family of protein phosphatase 2A (PP2A) is an important PP2A family involved in diverse cellular processes, and uniquely regulated by calcium binding to the regulatory subunit. The PR70 subunit in this family interacts with cell division control 6 (Cdc6), a cell cycle regulator important for control of DNA replication. Here, we report crystal structures of the isolated PR72 and the trimeric PR70 holoenzyme at a resolution of 2.1 and 2.4 A, respectively, and in vitro characterization of Cdc6 dephosphorylation. The holoenzyme structure reveals that one of the PR70 calcium-binding motifs directly contacts the scaffold subunit, resulting in the most compact scaffold subunit conformation among all PP2A holoenzymes. PR70 also binds distinctively to the catalytic subunit near the active site, which is required for PR70 to enhance phosphatase activity toward Cdc6. Our studies provide a structural basis for unique regulation of B/PR72 holoenzymes by calcium ions, and suggest the mechanisms for precise control of substrate specificity among PP2A holoenzymes.

Structure of the Ca(2+)-dependent PP2A heterotrimer and insights into Cdc6 dephosphorylation.,Wlodarchak N, Guo F, Satyshur KA, Jiang L, Jeffrey PD, Sun T, Stanevich V, Mumby MC, Xing Y Cell Res. 2013 Jul;23(7):931-46. doi: 10.1038/cr.2013.77. Epub 2013 Jun 11. PMID:23752926^[2]

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

References

↑ Bicknell LS, Bongers EM, Leitch A, Brown S, Schoots J, Harley ME, Aftimos S, Al-Aama JY, Bober M, Brown PA, van Bokhoven H, Dean J, Edrees AY, Feingold M, Fryer A, Hoefsloot LH, Kau N, Knoers NV, Mackenzie J, Opitz JM, Sarda P, Ross A, Temple IK, Toutain A, Wise CA, Wright M, Jackson AP. Mutations in the pre-replication complex cause Meier-Gorlin syndrome. Nat Genet. 2011 Feb 27;43(4):356-9. doi: 10.1038/ng.775. PMID:21358632 doi:10.1038/ng.775
↑ Wlodarchak N, Guo F, Satyshur KA, Jiang L, Jeffrey PD, Sun T, Stanevich V, Mumby MC, Xing Y. Structure of the Ca(2+)-dependent PP2A heterotrimer and insights into Cdc6 dephosphorylation. Cell Res. 2013 Jul;23(7):931-46. doi: 10.1038/cr.2013.77. Epub 2013 Jun 11. PMID:23752926 doi:10.1038/cr.2013.77

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/4i5n"

@@ Line 8: / Line 8: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4i5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i5n OCA], [https://pdbe.org/4i5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i5n RCSB], [https://www.ebi.ac.uk/pdbsum/4i5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i5n ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/CDC6_HUMAN CDC6_HUMAN] Defects in CDC6 are the cause of Meier-Gorlin syndrome type 5 (MGORS5) [MIM:[https://omim.org/entry/613805 613805]. MGORS5 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.<ref>PMID:21358632</ref>
 == Function ==
-[https://www.uniprot.org/uniprot/2AAA_HUMAN 2AAA_HUMAN] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.<ref>PMID:16580887</ref>
+[https://www.uniprot.org/uniprot/P2R3B_HUMAN P2R3B_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.[https://www.uniprot.org/uniprot/CDC6_HUMAN CDC6_HUMAN] Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4i5n

From Proteopedia

Current revision

Structural mechanism of trimeric PP2A holoenzyme involving PR70: insight for Cdc6 dephosphorylation

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

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