The Disintegrin-like Domain of the Snake Venom Metalloprotease Alternagin Inhibits α2β1 Integrin-Mediated Cell Adhesion

• Published in: Archives of biochemistry and biophysics 2000-12, Vol.384 (2), p.341-350
• Main Authors: Souza, D.H.F., Iemma, M.R.C., Ferreira, L.L., Faria, J.P., Oliva, M.L.V., Zingali, R.B., Niewiarowski, S., Selistre-de-Araujo, H.S.
• Format: Article
• Language: English
• Subjects: cell adhesion; collagen; disintegrin; metalloprotease; snake venom; α2β1 in tegrin
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1006/abbi.2000.2120

The α2β1 integrin is a major collagen receptor that plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Here we describe the isolation of a novel metalloproteinase/disintegrin, which is a potent inhibitor of the collagen binding to α2β1 integrin. This 55-kDa protein (alternagin) and its disintegrin domain (alternagin-C) were isolated from Bothrops alternatus snake venom. Amino acid sequencing of alternagin-C revealed the disintegrin structure. Alternagin and alternagin-C inhibit collagen I-mediated adhesion of K562-α2β1-transfected cells. The IC50 was 134 and 100 nM for alternagin and alternagin-C, respectively. Neither protein interfered with the adhesion of cells expressing αIIbβ3, α1β1, α5β1, α4β1 αVβ3, and α9β1 integrins to other ligands such as fibrinogen, fibronectin, and collagen IV. Alternagin and alternagin-C also mediated the adhesion of the K562-α2β1-transfected cells. Our results show that the disintegrin-like domain of alternagin is responsible for its ability to inhibit collagen binding to α2β1 integrin.