5jyq

Structural highlights

Function

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).^{[1] [2] [3]}

See Also

• Insulin 3D Structures

References

1. ↑ Safavi-Hemami H, Gajewiak J, Karanth S, Robinson SD, Ueberheide B, Douglass AD, Schlegel A, Imperial JS, Watkins M, Bandyopadhyay PK, Yandell M, Li Q, Purcell AW, Norton RS, Ellgaard L, Olivera BM. Specialized insulin is used for chemical warfare by fish-hunting cone snails. Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1743-8. PMID:25605914 doi:10.1073/pnas.1423857112
2. ↑ 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. A minimized human insulin-receptor-binding motif revealed in a Conus geographus venom insulin. Nat Struct Mol Biol. 2016 Sep 12. doi: 10.1038/nsmb.3292. PMID:27617429 doi:http://dx.doi.org/10.1038/nsmb.3292
3. ↑ Ahorukomeye P, Disotuar MM, Gajewiak J, Karanth S, Watkins M, Robinson SD, Flórez Salcedo P, Smith NA, Smith BJ, Schlegel A, Forbes BE, Olivera B, Hung-Chieh Chou D, Safavi-Hemami H. Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor. Elife. 2019 Feb 12;8:e41574. PMID:30747102 doi:10.7554/eLife.41574
4. ↑ 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. A minimized human insulin-receptor-binding motif revealed in a Conus geographus venom insulin. Nat Struct Mol Biol. 2016 Sep 12. doi: 10.1038/nsmb.3292. PMID:27617429 doi:http://dx.doi.org/10.1038/nsmb.3292