7nsc

From Proteopedia

(Difference between revisions)

Current revision

Substrate receptor scaffolding module of human CTLH E3 ubiquitin ligase

Structural highlights

7nsc is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RANB9_HUMAN May act as an adapter protein to couple membrane receptors to intracellular signaling pathways. May be involved in signaling of ITGB2/LFA-1 and other integrins. Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway. Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation. Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity. Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA (By similarity).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

How are E3 ubiquitin ligases configured to match substrate quaternary structures? Here, by studying the yeast GID complex (mutation of which causes deficiency in glucose-induced degradation of gluconeogenic enzymes), we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryoelectron microscopy (cryo-EM) structures show that, to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two minimally functional GID E3s assemble into the 20-protein Chelator-GID(SR4), which resembles an organometallic supramolecular chelate. The Chelator-GID(SR4) assembly avidly binds multiple Fbp1 degrons so that multiple Fbp1 protomers are simultaneously ubiquitylated at lysines near the allosteric and substrate binding sites. Importantly, key structural and biochemical features, including capacity for supramolecular assembly, are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical, and cell biological data, we propose that higher-order E3 ligase assembly generally enables multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.

GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme.,Sherpa D, Chrustowicz J, Qiao S, Langlois CR, Hehl LA, Gottemukkala KV, Hansen FM, Karayel O, von Gronau S, Prabu JR, Mann M, Alpi AF, Schulman BA Mol Cell. 2021 Apr 22. pii: S1097-2765(21)00220-3. doi:, 10.1016/j.molcel.2021.03.025. PMID:33905682^[8]

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

References

↑ Wang D, Li Z, Messing EM, Wu G. Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM. J Biol Chem. 2002 Sep 27;277(39):36216-22. Epub 2002 Jul 29. PMID:12147692 doi:http://dx.doi.org/10.1074/jbc.M205111200
↑ Rao MA, Cheng H, Quayle AN, Nishitani H, Nelson CC, Rennie PS. RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor. J Biol Chem. 2002 Dec 13;277(50):48020-7. Epub 2002 Oct 1. PMID:12361945 doi:http://dx.doi.org/10.1074/jbc.M209741200
↑ Zou Y, Lim S, Lee K, Deng X, Friedman E. Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M. J Biol Chem. 2003 Dec 5;278(49):49573-81. Epub 2003 Sep 18. PMID:14500717 doi:http://dx.doi.org/10.1074/jbc.M307556200
↑ Denti S, Sirri A, Cheli A, Rogge L, Innamorati G, Putignano S, Fabbri M, Pardi R, Bianchi E. RanBPM is a phosphoprotein that associates with the plasma membrane and interacts with the integrin LFA-1. J Biol Chem. 2004 Mar 26;279(13):13027-34. Epub 2004 Jan 13. PMID:14722085 doi:http://dx.doi.org/10.1074/jbc.M313515200
↑ Menon RP, Gibson TJ, Pastore A. The C terminus of fragile X mental retardation protein interacts with the multi-domain Ran-binding protein in the microtubule-organising centre. J Mol Biol. 2004 Oct 8;343(1):43-53. PMID:15381419 doi:http://dx.doi.org/10.1016/j.jmb.2004.08.024
↑ Kramer S, Ozaki T, Miyazaki K, Kato C, Hanamoto T, Nakagawara A. Protein stability and function of p73 are modulated by a physical interaction with RanBPM in mammalian cultured cells. Oncogene. 2005 Jan 27;24(5):938-44. PMID:15558019 doi:http://dx.doi.org/1208257
↑ Harada N, Yokoyama T, Yamaji R, Nakano Y, Inui H. RanBP10 acts as a novel coactivator for the androgen receptor. Biochem Biophys Res Commun. 2008 Mar 28;368(1):121-5. doi:, 10.1016/j.bbrc.2008.01.072. Epub 2008 Jan 24. PMID:18222118 doi:http://dx.doi.org/10.1016/j.bbrc.2008.01.072
↑ Sherpa D, Chrustowicz J, Qiao S, Langlois CR, Hehl LA, Gottemukkala KV, Hansen FM, Karayel O, von Gronau S, Prabu JR, Mann M, Alpi AF, Schulman BA. GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme. Mol Cell. 2021 Apr 22. pii: S1097-2765(21)00220-3. doi:, 10.1016/j.molcel.2021.03.025. PMID:33905682 doi:http://dx.doi.org/10.1016/j.molcel.2021.03.025

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/7nsc"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7nsc is ON HOLD
+==Substrate receptor scaffolding module of human CTLH E3 ubiquitin ligase==
+<StructureSection load='7nsc' size='340' side='right'caption='[[7nsc]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7nsc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NSC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NSC FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</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=7nsc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nsc OCA], [https://pdbe.org/7nsc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nsc RCSB], [https://www.ebi.ac.uk/pdbsum/7nsc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nsc ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/RANB9_HUMAN RANB9_HUMAN] May act as an adapter protein to couple membrane receptors to intracellular signaling pathways. May be involved in signaling of ITGB2/LFA-1 and other integrins. Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway. Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation. Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity. Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA (By similarity).<ref>PMID:12147692</ref> <ref>PMID:12361945</ref> <ref>PMID:14500717</ref> <ref>PMID:14722085</ref> <ref>PMID:15381419</ref> <ref>PMID:15558019</ref> <ref>PMID:18222118</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+How are E3 ubiquitin ligases configured to match substrate quaternary structures? Here, by studying the yeast GID complex (mutation of which causes deficiency in glucose-induced degradation of gluconeogenic enzymes), we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryoelectron microscopy (cryo-EM) structures show that, to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two minimally functional GID E3s assemble into the 20-protein Chelator-GID(SR4), which resembles an organometallic supramolecular chelate. The Chelator-GID(SR4) assembly avidly binds multiple Fbp1 degrons so that multiple Fbp1 protomers are simultaneously ubiquitylated at lysines near the allosteric and substrate binding sites. Importantly, key structural and biochemical features, including capacity for supramolecular assembly, are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical, and cell biological data, we propose that higher-order E3 ligase assembly generally enables multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.
-Authors:
+GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme.,Sherpa D, Chrustowicz J, Qiao S, Langlois CR, Hehl LA, Gottemukkala KV, Hansen FM, Karayel O, von Gronau S, Prabu JR, Mann M, Alpi AF, Schulman BA Mol Cell. 2021 Apr 22. pii: S1097-2765(21)00220-3. doi:, 10.1016/j.molcel.2021.03.025. PMID:33905682<ref>PMID:33905682</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7nsc" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Chrustowicz J]]
+[[Category: Prabu JR]]
+[[Category: Schulman BA]]
+[[Category: Sherpa D]]

7nsc

From Proteopedia

Current revision

Substrate receptor scaffolding module of human CTLH E3 ubiquitin ligase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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