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4psi

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Revision as of 22:21, 5 August 2016

PIH1D1/phospho-Tel2 complex

Structural highlights

4psi 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.
NonStd Res:	,
Related:	4psf
Gene:	PIH1D1, NOP17 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TELO2_HUMAN] Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals. May be involved in telomere length regulation.^[1] ^[2]

Publication Abstract from PubMed

The R2TP cochaperone complex plays a critical role in the assembly of multisubunit machines, including small nucleolar ribonucleoproteins (snoRNPs), RNA polymerase II, and the mTORC1 and SMG1 kinase complexes, but the molecular basis of substrate recognition remains unclear. Here, we describe a phosphopeptide binding domain (PIH-N) in the PIH1D1 subunit of the R2TP complex that preferentially binds to highly acidic phosphorylated proteins. A cocrystal structure of a PIH-N domain/TEL2 phosphopeptide complex reveals a highly specific phosphopeptide recognition mechanism in which Lys57 and 64 in PIH1D1, along with a conserved DpSDD phosphopeptide motif within TEL2, are essential and sufficient for binding. Proteomic analysis of PIH1D1 interactors identified R2TP complex substrates that are recruited by the PIH-N domain in a sequence-specific and phosphorylation-dependent manner suggestive of a common mechanism of substrate recognition. We propose that protein complexes assembled by the R2TP complex are defined by phosphorylation of a specific motif and recognition by the PIH1D1 subunit.

Phosphorylation-Dependent PIH1D1 Interactions Define Substrate Specificity of the R2TP Cochaperone Complex.,Horejsi Z, Stach L, Flower TG, Joshi D, Flynn H, Skehel JM, O'Reilly NJ, Ogrodowicz RW, Smerdon SJ, Boulton SJ Cell Rep. 2014 Apr 10;7(1):19-26. doi: 10.1016/j.celrep.2014.03.013. Epub 2014, Mar 20. PMID:24656813^[3]

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

References

↑ Jiang N, Benard CY, Kebir H, Shoubridge EA, Hekimi S. Human CLK2 links cell cycle progression, apoptosis, and telomere length regulation. J Biol Chem. 2003 Jun 13;278(24):21678-84. Epub 2003 Mar 31. PMID:12670948 doi:http://dx.doi.org/10.1074/jbc.M300286200
↑ Hurov KE, Cotta-Ramusino C, Elledge SJ. A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability. Genes Dev. 2010 Sep 1;24(17):1939-50. doi: 10.1101/gad.1934210. PMID:20810650 doi:http://dx.doi.org/10.1101/gad.1934210
↑ Horejsi Z, Stach L, Flower TG, Joshi D, Flynn H, Skehel JM, O'Reilly NJ, Ogrodowicz RW, Smerdon SJ, Boulton SJ. Phosphorylation-Dependent PIH1D1 Interactions Define Substrate Specificity of the R2TP Cochaperone Complex. Cell Rep. 2014 Apr 10;7(1):19-26. doi: 10.1016/j.celrep.2014.03.013. Epub 2014, Mar 20. PMID:24656813 doi:http://dx.doi.org/10.1016/j.celrep.2014.03.013

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4psi"

@@ Line 1: / Line 1: @@
 ==PIH1D1/phospho-Tel2 complex==
 <StructureSection load='4psi' size='340' side='right' caption='[[4psi]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4psf|4psf]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIH1D1, NOP17 ([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=4psi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4psi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4psi RCSB], [http://www.ebi.ac.uk/pdbsum/4psi PDBsum]</span></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=4psi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4psi OCA], [http://pdbe.org/4psi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4psi RCSB], [http://www.ebi.ac.uk/pdbsum/4psi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4psi ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4psi" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4psi

From Proteopedia

Revision as of 22:21, 5 August 2016

PIH1D1/phospho-Tel2 complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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