5u1m

From Proteopedia

(Difference between revisions)

Current revision

Structure of the IRS-1 PTB Domain Bound to the Juxtamembrane Region of the Insulin Receptor

Structural highlights

5u1m is a 2 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:	X-ray diffraction, Resolution 1.8Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IRS1_HUMAN Polymorphisms in IRS1 may be involved in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853.^[1] ^[2] ^[3] ^[4] ^[5]

Function

IRS1_HUMAN May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).^[6] ^[7]

Publication Abstract from PubMed

Despite a high degree of homology, insulin receptor (IR) and IGF-1 receptor (IGF1R) mediate distinct cellular and physiological functions. Here, we demonstrate how domain differences between IR and IGF1R contribute to the distinct functions of these receptors using chimeric and site-mutated receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to their higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation. Strikingly, replacement of leucine973 in the juxtamembrane region of IR to phenylalanine, which is present in IGF1R, mimics many of these signalling and gene expression responses. Overall, we show that the distinct activities of the closely related IR and IGF1R are mediated by their intracellular juxtamembrane region and substrate binding to this region.

Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression.,Cai W, Sakaguchi M, Kleinridders A, Gonzalez-Del Pino G, Dreyfuss JM, O'Neill BT, Ramirez AK, Pan H, Winnay JN, Boucher J, Eck MJ, Kahn CR Nat Commun. 2017 Mar 27;8:14892. doi: 10.1038/ncomms14892. PMID:28345670^[8]

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

References

↑ Federici M, Pandolfi A, De Filippis EA, Pellegrini G, Menghini R, Lauro D, Cardellini M, Romano M, Sesti G, Lauro R, Consoli A. G972R IRS-1 variant impairs insulin regulation of endothelial nitric oxide synthase in cultured human endothelial cells. Circulation. 2004 Jan 27;109(3):399-405. Epub 2004 Jan 5. PMID:14707024 doi:10.1161/01.CIR.0000109498.77895.6F
↑ Esposito DL, Mammarella S, Ranieri A, Della Loggia F, Capani F, Consoli A, Mariani-Costantini R, Caramia FG, Cama A, Battista P. Deletion of Gly723 in the insulin receptor substrate-1 of a patient with noninsulin-dependent diabetes mellitus. Hum Mutat. 1996;7(4):364-6. PMID:8723689 doi:<364::AID-HUMU13>3.0.CO;2-0 10.1002/(SICI)1098-1004(1996)7:4<364::AID-HUMU13>3.0.CO;2-0
↑ Mammarella S, Creati B, Esposito DL, Arcuri P, Della Loggia F, Capani F, Mariani-Costantini R, Caramia FG, Battista P, Cama A. Novel allele of the insulin receptor substrate-1 bearing two non-conservative amino acid substitutions in a patient with noninsulin-dependent diabetes mellitus. Mutations in brief no. 130. Online. Hum Mutat. 1998;11(5):411. PMID:10206679 doi:<411::AID-HUMU11>3.0.CO;2-2 10.1002/(SICI)1098-1004(1998)11:5<411::AID-HUMU11>3.0.CO;2-2
↑ Marini MA, Frontoni S, Mineo D, Bracaglia D, Cardellini M, De Nicolais P, Baroni A, D'Alfonso R, Perna M, Lauro D, Federici M, Gambardella S, Lauro R, Sesti G. The Arg972 variant in insulin receptor substrate-1 is associated with an atherogenic profile in offspring of type 2 diabetic patients. J Clin Endocrinol Metab. 2003 Jul;88(7):3368-71. PMID:12843189
↑ McGettrick AJ, Feener EP, Kahn CR. Human insulin receptor substrate-1 (IRS-1) polymorphism G972R causes IRS-1 to associate with the insulin receptor and inhibit receptor autophosphorylation. J Biol Chem. 2005 Feb 25;280(8):6441-6. Epub 2004 Dec 7. PMID:15590636 doi:10.1074/jbc.M412300200
↑ Kuo AH, Stoica GE, Riegel AT, Wellstein A. Recruitment of insulin receptor substrate-1 and activation of NF-kappaB essential for midkine growth signaling through anaplastic lymphoma kinase. Oncogene. 2007 Feb 8;26(6):859-69. Epub 2006 Jul 31. PMID:16878150 doi:10.1038/sj.onc.1209840
↑ Federici M, Pandolfi A, De Filippis EA, Pellegrini G, Menghini R, Lauro D, Cardellini M, Romano M, Sesti G, Lauro R, Consoli A. G972R IRS-1 variant impairs insulin regulation of endothelial nitric oxide synthase in cultured human endothelial cells. Circulation. 2004 Jan 27;109(3):399-405. Epub 2004 Jan 5. PMID:14707024 doi:10.1161/01.CIR.0000109498.77895.6F
↑ Cai W, Sakaguchi M, Kleinridders A, Gonzalez-Del Pino G, Dreyfuss JM, O'Neill BT, Ramirez AK, Pan H, Winnay JN, Boucher J, Eck MJ, Kahn CR. Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression. Nat Commun. 2017 Mar 27;8:14892. doi: 10.1038/ncomms14892. PMID:28345670 doi:http://dx.doi.org/10.1038/ncomms14892

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5u1m"

Categories: Homo sapiens | Large Structures | Dhe-Paganon S | Eck MJ

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5u1m is ON HOLD
+==Structure of the IRS-1 PTB Domain Bound to the Juxtamembrane Region of the Insulin Receptor==
+<StructureSection load='5u1m' size='340' side='right'caption='[[5u1m]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5u1m]] is a 2 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=5U1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U1M FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=5u1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u1m OCA], [https://pdbe.org/5u1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u1m RCSB], [https://www.ebi.ac.uk/pdbsum/5u1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u1m ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/IRS1_HUMAN IRS1_HUMAN] Polymorphisms in IRS1 may be involved in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[https://omim.org/entry/125853 125853].<ref>PMID:14707024</ref> <ref>PMID:8723689</ref> <ref>PMID:10206679</ref> <ref>PMID:12843189</ref> <ref>PMID:15590636</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/IRS1_HUMAN IRS1_HUMAN] May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).<ref>PMID:16878150</ref> <ref>PMID:14707024</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Despite a high degree of homology, insulin receptor (IR) and IGF-1 receptor (IGF1R) mediate distinct cellular and physiological functions. Here, we demonstrate how domain differences between IR and IGF1R contribute to the distinct functions of these receptors using chimeric and site-mutated receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to their higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation. Strikingly, replacement of leucine973 in the juxtamembrane region of IR to phenylalanine, which is present in IGF1R, mimics many of these signalling and gene expression responses. Overall, we show that the distinct activities of the closely related IR and IGF1R are mediated by their intracellular juxtamembrane region and substrate binding to this region.
-Authors: Eck, M.J., Dhe-Paganon, S.
+Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression.,Cai W, Sakaguchi M, Kleinridders A, Gonzalez-Del Pino G, Dreyfuss JM, O'Neill BT, Ramirez AK, Pan H, Winnay JN, Boucher J, Eck MJ, Kahn CR Nat Commun. 2017 Mar 27;8:14892. doi: 10.1038/ncomms14892. PMID:28345670<ref>PMID:28345670</ref>
-Description: Structure of the IRS-1 PTB Domain Bound to the Juxtamembrane Region of the Insulin Receptor
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Eck, M.J]]
+<div class="pdbe-citations 5u1m" style="background-color:#fffaf0;"></div>
-[[Category: Dhe-Paganon, S]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Dhe-Paganon S]]
+[[Category: Eck MJ]]

5u1m

From Proteopedia

Current revision

Structure of the IRS-1 PTB Domain Bound to the Juxtamembrane Region of the Insulin Receptor

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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