title: Isolation and characterization of three novel Gla-containing Conus marmoreus venom peptides, one with a novel cysteine pattern.
abstract: One defining characteristic of Conus venom peptides is the high frequency of posttranslational modifications found. We report the discovery and initial characterization of three novel gamma-carboxyglutamic acid (Gla)-containing conotoxins, Gla-MrII, Gla-MrIII, and Gla-MrIV, isolated from the venom of the mollusc-hunting cone snail Conus marmoreus. Peptide Gla-MrII, a 50 amino acid residue peptide, carries eight cysteine residues arranged in a novel cysteine pattern, and five gamma-carboxyglutamic acid residues. The monoisotopic molecular mass was determined by electrospray ionization mass spectrometry to 5860.23 Da, consistent with the peptide having the cysteine residues disulphide-bonded and having a free acid C-terminus. Peptides Gla-MrIII and Gla-MrIV each contain two gamma-carboxyglutamic acid residues and share little sequence similarity to previously identified conotoxins. Both peptides contain four cysteine residues that are positioned in the linear sequence in a manner reminiscent of conotoxins belonging to cysteine scaffold superfamily T (scaffold T-1). Determination of the monoisotopic molecular masses revealed that Gla-MrIII is amidated at its C-terminus while Gla-MrIV has a free C-terminal acid.
authors.affiliation: Department of Clinical Chemistry, Lund University, University Hospital, Malmö, S-20502 Malmö, Sweden. Karin.Hansson@klkemi.mas.lu.se
authors.forename: Karin
authors.initials: K
authors.lastname: Hansson
authors.forename: Bruce
authors.initials: B
authors.lastname: Furie
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Furie
authors.forename: Johan
authors.initials: J
authors.lastname: Stenflo
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins / Q000737:chemistry* / Q000235:genetics*; D003545:Cysteine; D008969:Molecular Sequence Data; D008970:Molecular Weight; D008978:Mollusk Venoms / Q000737:chemistry* / Q000235:genetics*; D010455:Peptides / Q000737:chemistry* / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012908:Snails; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D020916:Conotoxins; D008978:Mollusk Venoms; D010455:Peptides; C488194:conotoxin GlaMrII, Conus marmoreus; C488195:conotoxin GlaMrIII, Conus marmoreus; C488196:conotoxin GlaMrIV, Conus marmoreus; D015055:1-Carboxyglutamic Acid; D003545:Cysteine