5jyq: Difference between revisions
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==Structure of Conus Geographus insulin G1== | ==Structure of Conus Geographus insulin G1== | ||
<StructureSection load='5jyq' size='340' side='right' caption='[[5jyq]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='5jyq' size='340' side='right'caption='[[5jyq]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5jyq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JYQ OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5jyq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JYQ FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=CY3:2-AMINO-3-MERCAPTO-PROPIONAMIDE'>CY3</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5jyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jyq OCA], [https://pdbe.org/5jyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jyq RCSB], [https://www.ebi.ac.uk/pdbsum/5jyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jyq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/INS1A_CONGE INS1A_CONGE] This venom insulin, from a fish-hunting cone snail, facilitates prey capture by rapidly inducing hypoglycemic shock (PubMed:25605914, PubMed:27617429). It is one of the smallest known insulin found in nature and lacks the C-terminal segment of the B chain that, in human insulin, mediates engagement of the insulin receptor (INSR) and assembly of the hormone's hexameric storage form (PubMed:27617429). Despite lacking this segment, it both binds and activates human insulin receptor (long isoform (HIR-B)) with a high potency (EC(50)=16.28 nM) (PubMed:30747102, PubMed:27617429). In vivo, intraperitoneal injection of this peptide into zebrafish lowers blood glucose with the same potency than human insulin (PubMed:25605914, PubMed:30747102). In addition, when applied to water, this peptide reduces overall locomotor activity of zebrafish larvae, observed as a significant decrease in the percentage of time spent swimming and movement frequency (PubMed:25605914). When tested on a mouse model of diabetes, this insulin also lowers blood glucose with a 10-fold lower potency than human insulin (PubMed:30747102).<ref>PMID:25605914</ref> <ref>PMID:27617429</ref> <ref>PMID:30747102</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Insulins in the venom of certain fish-hunting cone snails facilitate prey capture by rapidly inducing hypoglycemic shock. One such insulin, Conus geographus G1 (Con-Ins G1), is the smallest known insulin found in nature and lacks the C-terminal segment of the B chain that, in human insulin, mediates engagement of the insulin receptor and assembly of the hormone's hexameric storage form. Removal of this segment (residues B23-B30) in human insulin results in substantial loss of receptor affinity. Here, we found that Con-Ins G1 is monomeric, strongly binds the human insulin receptor and activates receptor signaling. Con-Ins G1 thus is a naturally occurring B-chain-minimized mimetic of human insulin. Our crystal structure of Con-Ins G1 reveals a tertiary structure highly similar to that of human insulin and indicates how Con-Ins G1's lack of an equivalent to the key receptor-engaging residue PheB24 is mitigated. These findings may facilitate efforts to design ultrarapid-acting therapeutic insulins. | |||
A minimized human insulin-receptor-binding motif revealed in a Conus geographus venom insulin.,Menting JG, Gajewiak J, MacRaild CA, Chou DH, Disotuar MM, Smith NA, Miller C, Erchegyi J, Rivier JE, Olivera BM, Forbes BE, Smith BJ, Norton RS, Safavi-Hemami H, Lawrence MC Nat Struct Mol Biol. 2016 Sep 12. doi: 10.1038/nsmb.3292. PMID:27617429<ref>PMID:27617429</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5jyq" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Insulin 3D Structures|Insulin 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Conus geographus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Lawrence MC]] | ||
[[Category: | [[Category: Menting J]] | ||
[[Category: | [[Category: Norton RS]] | ||
[[Category: | [[Category: Safavi-Hemami H]] | ||
