PXD053107

PXD053107 is an original dataset announced via ProteomeXchange.

Title	Disruption of Glucose Homeostasis in Prey: Combinatorial Use of Weaponized Mimetics of Somatostatin and Insulin by a Fish-Hunting Cone Snail
Description	Venomous animals have evolved diverse molecular mechanisms to incapacitate prey and defend against predators. The majority of venom components characterized to date disrupt the nervous, locomotor, and cardiovascular system or causes tissue damage and degradation1. The discovery that certain species of fish-hunting cone snail use weaponized insulins to induce hypoglycemic shock in prey provided an unusual example for the use of toxins that target glucose homeostasis2. Here, we show that, in addition to insulins, the deadly fish hunter, Conus geographus, uses a selective agonist of the somatostatin receptor 2 (SSTR2) that potently blocks the release of the insulin-counteracting hormone glucagon, thereby exacerbating insulin-induced hypoglycemia in prey. The native toxin, Consomatin nG1, exists in several proteoforms that contain a minimized vertebrate somatostatin-like core motif connected to a heavily glycosylated N-terminal region. We demonstrate that the toxin’s N-terminal tail aligns with a glycosylated somatostatin peptide previously identified from fish pancreas and plays an important role in activating the fish SSTR2. Collectively, these findings provide a stunning example of chemical mimicry, highlight the combinatorial nature of venom components, and establish glucose homeostasis as an effective target for prey capture.
HostingRepository	PRIDE
AnnounceDate	2024-06-26
AnnouncementXML	Submission_2024-06-26_08:18:37.933.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD053107
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Thomas Koch
SpeciesList	scientific name: Conus geographus (Geography cone) (Nubecula geographus); NCBI TaxID: 6491;
ModificationList	amidated residue; 2-pyrrolidone-5-carboxylic acid (Gln); monohydroxylated residue; O-glycosyl-L-threonine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-14 03:24:12	ID requested
⏵ 1	2024-06-26 08:18:38	announced

10.6019/PXD053107;

submitter keyword: cabals, glycosylation, somatostatin, weaponized hormones, venom, chemical mimicry, glycopeptides, doppelganger peptide, toxins, cone snail, glucose homeostasis, insulin

Helena Safavi-Hemami
contact affiliation	Department of Biochemistry, University of Utah
contact email	helena.safavi@biochem.utah.edu
lab head
Thomas Koch
contact affiliation	University of Utah
contact email	thomas.lund.koch@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053107
     1. Label: PRIDE project
     2. Name: Disruption of Glucose Homeostasis in Prey: Combinatorial Use of Weaponized Mimetics of Somatostatin and Insulin by a Fish-Hunting Cone Snail