7u23
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7u23]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lymphocystis_disease_virus_1 Lymphocystis disease virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U23 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U23 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7u23]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lymphocystis_disease_virus_1 Lymphocystis disease virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U23 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U23 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=7u23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u23 OCA], [https://pdbe.org/7u23 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u23 RCSB], [https://www.ebi.ac.uk/pdbsum/7u23 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u23 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.6Å</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=7u23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u23 OCA], [https://pdbe.org/7u23 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u23 RCSB], [https://www.ebi.ac.uk/pdbsum/7u23 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u23 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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Lymphocystis disease virus-1 (LCDV-1) and several other Iridoviridae encode viral insulin/IGF-1 like peptides (VILPs) with high homology to human insulin and IGFs. Here we show that while single-chain (sc) and double-chain (dc) LCDV1-VILPs have very low affinity for the insulin receptor, scLCDV1-VILP has high affinity for IGF1R where it can antagonize human IGF-1 signaling, without altering insulin signaling. Consequently, scLCDV1-VILP inhibits IGF-1 induced cell proliferation and growth hormone/IGF-1 induced growth of mice in vivo. Cryo-electron microscopy reveals that scLCDV1-VILP engages IGF1R in a unique manner, inducing changes in IGF1R conformation that led to separation, rather than juxtaposition, of the transmembrane segments and hence inactivation of the receptor. Thus, scLCDV1-VILP is a natural peptide with specific antagonist properties on IGF1R signaling and may provide a new tool to guide development of hormonal analogues to treat cancers or metabolic disorders sensitive to IGF-1 without affecting glucose metabolism. | Lymphocystis disease virus-1 (LCDV-1) and several other Iridoviridae encode viral insulin/IGF-1 like peptides (VILPs) with high homology to human insulin and IGFs. Here we show that while single-chain (sc) and double-chain (dc) LCDV1-VILPs have very low affinity for the insulin receptor, scLCDV1-VILP has high affinity for IGF1R where it can antagonize human IGF-1 signaling, without altering insulin signaling. Consequently, scLCDV1-VILP inhibits IGF-1 induced cell proliferation and growth hormone/IGF-1 induced growth of mice in vivo. Cryo-electron microscopy reveals that scLCDV1-VILP engages IGF1R in a unique manner, inducing changes in IGF1R conformation that led to separation, rather than juxtaposition, of the transmembrane segments and hence inactivation of the receptor. Thus, scLCDV1-VILP is a natural peptide with specific antagonist properties on IGF1R signaling and may provide a new tool to guide development of hormonal analogues to treat cancers or metabolic disorders sensitive to IGF-1 without affecting glucose metabolism. | ||
| - | Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist.,Moreau F, Kirk NS, Zhang F, Gelfanov V, List EO, Chrudinova M, Venugopal H, Lawrence MC, Jimenez V, Bosch F, Kopchick JJ, DiMarchi RD, Altindis E, | + | Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist.,Moreau F, Kirk NS, Zhang F, Gelfanov V, List EO, Chrudinova M, Venugopal H, Lawrence MC, Jimenez V, Bosch F, Kopchick JJ, DiMarchi RD, Altindis E, Kahn CR Nat Commun. 2022 Nov 5;13(1):6700. doi: 10.1038/s41467-022-34391-6. PMID:36335114<ref>PMID:36335114</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Revision as of 11:36, 23 October 2024
Single-chain LCDV-1 viral insulin-like peptide bound to IGF-1R ectodomain, leucine-zippered form
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