<?xml version="1.0" encoding="UTF-8" standalone="yes"?> <ProteomeXchangeDataset id="PXD052869" formatVersion="1.4.0" xsi:noNamespaceSchemaLocation="proteomeXchange-1.4.0.xsd" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <CvList> <Cv fullName="PSI-MS" uri="https://raw.githubusercontent.com/HUPO-PSI/psi-ms-CV/master/psi-ms.obo" id="MS"/> <Cv fullName="PSI-MOD" uri="https://raw.githubusercontent.com/MICommunity/psidev/master/psi/mod/data/PSI-MOD.obo" id="MOD"/> <Cv fullName="UNIMOD" uri="http://www.unimod.org/obo/unimod.obo" id="UNIMOD"/> </CvList> <DatasetSummary announceDate="2024-06-26" hostingRepository="PRIDE" 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 degradation. 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 homeostasis. 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.</Description> <ReviewLevel> <cvParam cvRef="MS" accession="MS:1002854" name="Peer-reviewed dataset"/> </ReviewLevel> <RepositorySupport> <cvParam cvRef="MS" accession="MS:1002856" name="Supported dataset by repository"/> </RepositorySupport> </DatasetSummary> <DatasetIdentifierList> <DatasetIdentifier> <cvParam cvRef="MS" accession="MS:1001919" name="ProteomeXchange accession number" value="PXD052869"/> </DatasetIdentifier> <DatasetIdentifier> <cvParam cvRef="MS" accession="MS:1001922" name="Digital Object Identifier (DOI)" value="10.6019/PXD052869"/> </DatasetIdentifier> </DatasetIdentifierList> <DatasetOriginList> <DatasetOrigin> <cvParam cvRef="MS" accession="MS:1002868" name="Original data"/> </DatasetOrigin> </DatasetOriginList> <SpeciesList> <Species> <cvParam cvRef="MS" accession="MS:1001469" name="taxonomy: scientific name" value="Conus geographus (Geography cone) (Nubecula geographus)"/> <cvParam cvRef="MS" accession="MS:1001467" name="taxonomy: NCBI TaxID" value="6491"/> </Species> </SpeciesList> <InstrumentList> <Instrument id="Instrument_1"> <cvParam cvRef="MS" accession="MS:1002416" name="Orbitrap Fusion"/> </Instrument> </InstrumentList> <ModificationList> <cvParam cvRef="MOD" accession="MOD:00398" name="carbamoylated residue"/> <cvParam cvRef="MOD" accession="MOD:00674" name="amidated residue"/> <cvParam cvRef="MOD" accession="MOD:00040" name="2-pyrrolidone-5-carboxylic acid (Gln)"/> <cvParam cvRef="MOD" accession="MOD:00425" name="monohydroxylated residue"/> <cvParam cvRef="MOD" accession="MOD:00005" name="O-glycosyl-L-threonine"/> </ModificationList> <ContactList> <Contact id="project_submitter"> <cvParam cvRef="MS" accession="MS:1000586" name="contact name" value="Thomas Koch"/> <cvParam cvRef="MS" accession="MS:1000589" name="contact email" value="thomas.lund.koch@gmail.com"/> <cvParam cvRef="MS" accession="MS:1000590" name="contact affiliation" value="University of Utah"/> <cvParam cvRef="MS" accession="MS:1002037" name="dataset submitter"/> </Contact> <Contact id="project_lab_head"> <cvParam cvRef="MS" accession="MS:1002332" name="lab head"/> <cvParam cvRef="MS" accession="MS:1000586" name="contact name" value="Helena Safavi-Hemami"/> <cvParam cvRef="MS" accession="MS:1000589" name="contact email" value="helena.safavi@biochem.utah.edu"/> <cvParam cvRef="MS" accession="MS:1000590" name="contact affiliation" value="Department of Biochemistry, University of Utah"/> </Contact> </ContactList> <PublicationList> <Publication id="DOI-10_6019_PXD052869"> <cvParam cvRef="MS" accession="MS:1001922" name="Digital Object Identifier (DOI)" value="10.6019/PXD052869"/> </Publication> </PublicationList> <KeywordList> <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="cabals, glycosylation, somatostatin, weaponized hormones, venom, chemical mimicry, glycopeptides, doppelganger peptide, toxins, cone snail, glucose homeostasis, insulin"/> </KeywordList> <FullDatasetLinkList> <FullDatasetLink> <cvParam cvRef="MS" accession="MS:1002852" name="Dataset FTP location" value="ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD052869"/> </FullDatasetLink> <FullDatasetLink> <cvParam cvRef="MS" accession="MS:1001930" name="PRIDE project URI" value="http://www.ebi.ac.uk/pride/archive/projects/PXD052869"/> </FullDatasetLink> </FullDatasetLinkList> <DatasetFileList> <DatasetFile id="FILE_1" name="ng1-resubmission50.mzid.gz"> <cvParam cvRef="MS" accession="MS:1002848" name="Result file URI" value="ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD052869/ng1-resubmission50.mzid.gz"/> </DatasetFile> <DatasetFile id="FILE_2" name="ng1.fasta"> <cvParam cvRef="MS" accession="MS:1002845" name="Associated file URI" value="ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD052869/ng1.fasta"/> 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