Leberagin-C, A disintegrin-like/cysteine-rich protein from Macrovipera lebetina transmediterranea venom, inhibits alphavbeta3 integrin-mediated cell adhesion

详细信息    查看全文

• 作者：Inè ; s Limam ; Amine Bazaa ; Najet Srairi-Abid ; Salma Taboubi ; Jed Jebali ; Raoudha Zouari-Kessentini ; Olfa Kallech-Ziri ; Hafedh Mejdoub ; Asma Hammami ; Mohamed El Ayeb ; José ; Luis ; Naziha Marrakch
• 关键词：Disintegrin-like/cysteine-rich domain ; cDNA ; Model ; Platelet ; Cell adhesion ; Alphavbeta3 ; Integrins
• 刊名：Matrix Biology
• 出版年：2010
• 出版时间：March 2010
• 年：2010
• 卷：29
• 期：2
• 页码：117-126
• 全文大小：712 K

文摘

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 IC₅₀ 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.