title: Leberagin-C, A disintegrin-like/cysteine-rich protein from Macrovipera lebetina transmediterranea venom, inhibits alphavbeta3 integrin-mediated cell adhesion.
abstract: Leberagin-C, a new member of the disintegrin-like/cysteine-rich (D/C) family, was purified to homogeneity from the venom of Tunisian snake Macrovipera lebetina transmediterranea. It is a monomeric protein with a molecular mass of 25,787 Da. Its complete sequence of 205 amino acid residues was established by cDNA cloning. The leberagin-C shows many conserved sequences with other known D/C proteins, like the SECD binding sites and a pattern of 28 cysteines. It is the first purified protein from M. lebetina transmediterranea with only two disintegrin-like/cysteine-rich domains. Leberagin-C is able to inhibit platelet aggregation induced by thrombin and arachidonic acid with IC(50) of 40 and 50 nM respectively. It was also able to inhibit the adhesion of melanoma tumour cells on fibrinogen and fibronectin, by interfering with the function of alphavbeta3 and, to a lesser extent, with alphavbeta6 and alpha5beta1 integrins. To our knowledge, leberagin-C is the sole described D/C protein that does not specifically interact with the alpha2beta1 integrin. Structure-activity relationship study of leberagin-C suggested that there are some important amino acid differences with jararhagin, the most studied PIII metalloprotease from Bothrops jararaca, notably around the SECD motif in its disintegrin-like domain. Other regions implicated in leberagin-C specificities could not be excluded.
authors.affiliation: Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Tunis Belvédère, Tunisia. limem_iness@yahoo.fr
authors.forename: Inès
authors.initials: I
authors.lastname: Limam
authors.forename: Amine
authors.initials: A
authors.lastname: Bazaa
authors.forename: Najet
authors.initials: N
authors.lastname: Srairi-Abid
authors.forename: Salma
authors.initials: S
authors.lastname: Taboubi
authors.forename: Jed
authors.initials: J
authors.lastname: Jebali
authors.forename: Raoudha
authors.initials: R
authors.lastname: Zouari-Kessentini
authors.forename: Olfa
authors.initials: O
authors.lastname: Kallech-Ziri
authors.forename: Hafedh
authors.initials: H
authors.lastname: Mejdoub
authors.forename: Asma
authors.initials: A
authors.lastname: Hammami
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Ayeb
authors.forename: José
authors.initials: J
authors.lastname: Luis
authors.forename: Naziha
authors.initials: N
authors.lastname: Marrakchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D003545:Cysteine / Q000378:metabolism; D019483:Disintegrins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014757:Viper Venoms / Q000737:chemistry* / Q000235:genetics; D017819:Viperidae
chemical_list: D000951:Antigens, Neoplasm; D019483:Disintegrins; D038982:Integrin alpha2beta1; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D016023:Integrins; D010975:Platelet Aggregation Inhibitors; D014757:Viper Venoms; C073878:integrin alphavbeta6; D003545:Cysteine