title: Terminal disialylated multiantennary complex-type N-glycans carried on acutobin define the glycosylation characteristics of the Deinagkistrodon acutus venom.
abstract: Glycosylation analysis of nonmammalian sources often springs surprises and conjures up intriguing views of evolutionary adaptation. Many of the constituents of snake venoms are known to be glycosylated and yet very few were fully characterized and accorded specific functions. In the process of glycomic screening through the venoms from Asian pit vipers, a partially O-acetylated NeuAcα2-8NeuAcα2-3Galβ1-4GlcNAcβ1-terminal epitope was found to be the predominant glycosylation characteristic of the snake venom produced by the monotypic Deinagkistrodon acutus, with acutobin, a highly specific fibrinogenase, being identified as a primary protein carrier. Full structural definition and glycosylation site mapping were completed through advanced mass spectrometry analyses at both the glycan and glycopeptide levels in conjunction with chemical and enzymatic cleavages. Although similar occurrence of such terminal disialyl cap on the N-glycans of several mammalian glycoproteins has been implicated, most of these correspond to only minor constituents of the full glycomic heterogeneity and remain poorly characterized. In contrast, each antennae of the hybrid- and complex-type N-glycans derived from acutobin was found to be rather homogeneously disialylated. With up to eight sialic acids evenly distributed on nonextended tetraantennary core structure, these unusual N-glycans are among those of highest sialic acid density ever identified without actually carrying polysialic acid chains. It remains to be tested whether they may serve as multivalent disialyl ligands for several of the human Siglecs and thus meddle with the natural immuno-recognition systems of snakebite victims, apart from affecting the general efficacy of acutobin as anticoagulant in biomedical applications.
authors.affiliation: Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Lin
authors.forename: Jin-Mei
authors.initials: JM
authors.lastname: Chen
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Wang
authors.forename: Sz-Wei
authors.initials: SW
authors.lastname: Wu
authors.forename: Inn-Ho
authors.initials: IH
authors.lastname: Tsai
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
mesh_terms: D000595:Amino Acid Sequence; D000606:Amino Sugars / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002240:Carbohydrate Sequence; D003435:Crotalid Venoms / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D017839:Crotalus; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D025942:Oligosaccharides, Branched-Chain / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D013917:Thrombin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000606:Amino Sugars; D003435:Crotalid Venoms; D009844:Oligosaccharides; D025942:Oligosaccharides, Branched-Chain; D011134:Polysaccharides; D012794:Sialic Acids; C016735:sialooligosaccharides; C000458:N-acetyllactosamine; D013917:Thrombin; C508893:acutobin, Deinagkistrodon acutus