View source for 6vti


==Solution NMR structure of the N-terminal domain of the Serine/threonine-protein phosphatase 1 regulatory subunit 10, PPP1R10==
<StructureSection load='6vti' size='340' side='right'caption='[[6vti]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vti]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VTI FirstGlance]. <br>
</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=6vti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vti OCA], [https://pdbe.org/6vti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vti RCSB], [https://www.ebi.ac.uk/pdbsum/6vti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vti ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PP1RA_RAT PP1RA_RAT] Scaffold protein which mediates the formation of the PTW/PP1 phosphatase complex by providing a binding platform to each component of the complex. The PTW/PP1 phosphatase complex plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Mediates interaction of WDR82 and PPP1CA. Inhibitor of PPP1CA and PPP1CC phosphatase activities. Has inhibitory activity on PPP1CA only when phosphorylated. Binds to mRNA, single-stranded DNA (ssDNA), poly(A) and poly(G) homopolymers.<ref>PMID:9461602</ref> <ref>PMID:12574161</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Despite MYC dysregulation in most human cancers, strategies to target this potent oncogenic driver remain an urgent unmet need. Recent evidence shows the PP1 phosphatase and its regulatory subunit PNUTS control MYC phosphorylation, chromatin occupancy, and stability, however the molecular basis remains unclear. Here we demonstrate that MYC interacts directly with PNUTS through the MYC homology Box 0 (MB0), a highly conserved region recently shown to be important for MYC oncogenic activity. By NMR we identified a distinct peptide motif within MB0 that interacts with PNUTS residues 1-148, a functional unit, here termed PNUTS amino-terminal domain (PAD). Using NMR spectroscopy we determined the solution structure of PAD, and characterised its MYC-binding patch. Point mutations of residues at the MYC-PNUTS interface significantly weaken their interaction both in vitro and in vivo, leading to elevated MYC phosphorylation. These data demonstrate that the MB0 region of MYC directly interacts with the PAD of PNUTS, which provides new insight into the control mechanisms of MYC as a regulator of gene transcription and a pervasive cancer driver.

The MYC oncoprotein directly interacts with its chromatin cofactor PNUTS to recruit PP1 phosphatase.,Wei Y, Redel C, Ahlner A, Lemak A, Johansson-Akhe I, Houliston S, Kenney TMG, Tamachi A, Morad V, Duan S, Andrews DW, Wallner B, Sunnerhagen M, Arrowsmith CH, Penn LZ Nucleic Acids Res. 2022 Mar 4. pii: 6542486. doi: 10.1093/nar/gkac138. PMID:35244724<ref>PMID:35244724</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6vti" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Arrowsmith CH]]
[[Category: Duan S]]
[[Category: Houliston S]]
[[Category: Lemak A]]
[[Category: Penn LZ]]
[[Category: Wei Y]]