6ewx

From Proteopedia

(Difference between revisions)

Current revision

Structure of Pragmin pseudo-kinase reveals a dimerization mechanism to regulate protein tyrosine phosphorylation and nuclear transcription

Structural highlights

6ewx is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.771Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PRAG1_RAT Catalytically inactive protein kinase that acts as a scaffold protein (PubMed:29503074). Functions as an effector of the small GTPase RND2, which stimulates RhoA activity and inhibits NGF-induced neurite outgrowth (PubMed:16481321). Promotes Src family kinase (SFK) signallig by regulating the subcellular localization of CSK, a negative regulator of these kinases, leading to the regulation of cell morphology and motility by a CSK-dependent mechanism (PubMed:27116701, PubMed:21873224). Acts as a critical coactivator of Notch signaling (By similarity).[UniProtKB:Q571I4]^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The pseudo-kinase and signaling protein Pragmin has been linked to cancer by regulating protein tyrosine phosphorylation via unknown mechanisms. Here we present the crystal structure of the Pragmin 906-1,368 amino acid C terminus, which encompasses its kinase domain. We show that Pragmin contains a classical protein-kinase fold devoid of catalytic activity, despite a conserved catalytic lysine (K997). By proteomics, we discovered that this pseudo-kinase uses the tyrosine kinase CSK to induce protein tyrosine phosphorylation in human cells. Interestingly, the protein-kinase domain is flanked by N- and C-terminal extensions forming an original dimerization domain that regulates Pragmin self-association and stimulates CSK activity. A1329E mutation in the C-terminal extension destabilizes Pragmin dimerization and reduces CSK activation. These results reveal a dimerization mechanism by which a pseudo-kinase can induce protein tyrosine phosphorylation. Further sequence-structure analysis identified an additional member (C19orf35) of the superfamily of dimeric Pragmin/SgK269/PEAK1 pseudo-kinases.

Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation.,Lecointre C, Simon V, Kerneur C, Allemand F, Fournet A, Montarras I, Pons JL, Gelin M, Brignatz C, Urbach S, Labesse G, Roche S Structure. 2018 Apr 3;26(4):545-554.e4. doi: 10.1016/j.str.2018.01.017. Epub 2018, Mar 1. PMID:29503074^[5]

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

References

↑ Tanaka H, Katoh H, Negishi M. Pragmin, a novel effector of Rnd2 GTPase, stimulates RhoA activity. J Biol Chem. 2006 Apr 14;281(15):10355-64. PMID:16481321 doi:10.1074/jbc.M511314200
↑ Safari F, Murata-Kamiya N, Saito Y, Hatakeyama M. Mammalian Pragmin regulates Src family kinases via the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif that is exploited by bacterial effectors. Proc Natl Acad Sci U S A. 2011 Sep 6;108(36):14938-43. PMID:21873224 doi:10.1073/pnas.1107740108
↑ Senda Y, Murata-Kamiya N, Hatakeyama M. C-terminal Src kinase-mediated EPIYA phosphorylation of Pragmin creates a feed-forward C-terminal Src kinase activation loop that promotes cell motility. Cancer Sci. 2016 Jul;107(7):972-80. PMID:27116701 doi:10.1111/cas.12962
↑ Lecointre C, Simon V, Kerneur C, Allemand F, Fournet A, Montarras I, Pons JL, Gelin M, Brignatz C, Urbach S, Labesse G, Roche S. Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation. Structure. 2018 Apr 3;26(4):545-554.e4. doi: 10.1016/j.str.2018.01.017. Epub 2018, Mar 1. PMID:29503074 doi:http://dx.doi.org/10.1016/j.str.2018.01.017
↑ Lecointre C, Simon V, Kerneur C, Allemand F, Fournet A, Montarras I, Pons JL, Gelin M, Brignatz C, Urbach S, Labesse G, Roche S. Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation. Structure. 2018 Apr 3;26(4):545-554.e4. doi: 10.1016/j.str.2018.01.017. Epub 2018, Mar 1. PMID:29503074 doi:http://dx.doi.org/10.1016/j.str.2018.01.017

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/6ewx"

@@ Line 1: / Line 1: @@
 ==Structure of Pragmin pseudo-kinase reveals a dimerization mechanism to regulate protein tyrosine phosphorylation and nuclear transcription==
-<StructureSection load='6ewx' size='340' side='right' caption='[[6ewx]], [[Resolution|resolution]] 2.77&Aring;' scene=''>
+<StructureSection load='6ewx' size='340' side='right'caption='[[6ewx]], [[Resolution|resolution]] 2.77&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ewx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EWX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EWX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ewx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EWX FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.771&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Prag1, Pragmin, RGD1311793_predicted, rCG_43329 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6ewx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ewx OCA], [http://pdbe.org/6ewx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ewx RCSB], [http://www.ebi.ac.uk/pdbsum/6ewx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ewx 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=6ewx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ewx OCA], [https://pdbe.org/6ewx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ewx RCSB], [https://www.ebi.ac.uk/pdbsum/6ewx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ewx ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/PRAG1_RAT PRAG1_RAT] Catalytically inactive protein kinase that acts as a scaffold protein (PubMed:29503074). Functions as an effector of the small GTPase RND2, which stimulates RhoA activity and inhibits NGF-induced neurite outgrowth (PubMed:16481321). Promotes Src family kinase (SFK) signallig by regulating the subcellular localization of CSK, a negative regulator of these kinases, leading to the regulation of cell morphology and motility by a CSK-dependent mechanism (PubMed:27116701, PubMed:21873224). Acts as a critical coactivator of Notch signaling (By similarity).[UniProtKB:Q571I4]<ref>PMID:16481321</ref> <ref>PMID:21873224</ref> <ref>PMID:27116701</ref> <ref>PMID:29503074</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Buffalo rat]]
+[[Category: Large Structures]]
-[[Category: Allemand, F]]
+[[Category: Rattus norvegicus]]
-[[Category: Fournet, A]]
+[[Category: Allemand F]]
-[[Category: Gelin, M]]
+[[Category: Fournet A]]
-[[Category: Labesse, G]]
+[[Category: Gelin M]]
-[[Category: Cancer]]
+[[Category: Labesse G]]
-[[Category: Cell invasion]]
-[[Category: Pseudokinase]]
-[[Category: Scaffolding protein]]

6ewx

From Proteopedia

Current revision

Structure of Pragmin pseudo-kinase reveals a dimerization mechanism to regulate protein tyrosine phosphorylation and nuclear transcription

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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