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Leberagin-C, A disintegrin-like/cysteine-rich protein from Macrovipera lebetina transmediterranea venom, inhibits alphavbeta3 integrin-mediated cell adhesion
- Source :
- Matrix Biology, Matrix Biology, Elsevier, 2010, 29 (2), pp.117-26. ⟨10.1016/j.matbio.2009.09.009⟩
- Publication Year :
- 2010
- Publisher :
- HAL CCSD, 2010.
-
Abstract
- International audience; 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.
- Subjects :
- Models, Molecular
Integrins
Platelet Aggregation
Disintegrins
MESH: Viperidae
MESH: Antigens, Neoplasm
MESH: Amino Acid Sequence
MESH: Base Sequence
Conserved sequence
MESH: Protein Structure, Tertiary
Protein structure
Viperidae
MESH: Animals
Peptide sequence
MESH: Platelet Aggregation
0303 health sciences
biology
030302 biochemistry & molecular biology
MESH: Integrins
MESH: Integrin alphaVbeta3
Biochemistry
MESH: Platelet Aggregation Inhibitors
Jararhagin
Integrin alpha2beta1
MESH: Viper Venoms
Macrovipera lebetina
MESH: Models, Molecular
Integrin alpha5beta1
MESH: Cell Line, Tumor
Molecular Sequence Data
Integrin
MESH: Sequence Alignment
Viper Venoms
MESH: Cell Adhesion
03 medical and health sciences
Antigens, Neoplasm
Cell Line, Tumor
Cell Adhesion
Disintegrin
Animals
Humans
Amino Acid Sequence
Cysteine
MESH: Disintegrins
Cell adhesion
Molecular Biology
030304 developmental biology
MESH: Molecular Sequence Data
MESH: Humans
Base Sequence
MESH: Integrin alpha5beta1
MESH: Cysteine
Integrin alphaVbeta3
biology.organism_classification
Molecular biology
Protein Structure, Tertiary
biology.protein
Sequence Alignment
Platelet Aggregation Inhibitors
MESH: Integrin alpha2beta1
Subjects
Details
- Language :
- English
- ISSN :
- 0945053X
- Database :
- OpenAIRE
- Journal :
- Matrix Biology, Matrix Biology, Elsevier, 2010, 29 (2), pp.117-26. ⟨10.1016/j.matbio.2009.09.009⟩
- Accession number :
- edsair.doi.dedup.....8427f129741daba1456e25af6f74e81b