Contortrostatin, a Homodimeric Disintegrin, Binds to Integrin αvβ5

• Published in: Biochemical and biophysical research communications Vol. 267; no. 1; pp. 350 - 355
• Main Authors: Zhou, Qing, Nakada, Marian T., Brooks, Peter C., Swenson, Stephen D., Ritter, Matthew R., Argounova, Svetlana, Arnold, Catherine, Markland, Francis S.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 07.01.2000
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.1965

Contortrostatin is a homodimeric disintegrin from snake venom. We have shown that contortrostatin binds to integrins αIIbβ3, α5β1, and αvβ3. We now use several criteria to demonstrate the binding of contortrostatin to αvβ5. First, incubation of T24 cells, which express αvβ3 and αvβ5, with antibody against αvβ3 failed to completely inhibit adhesion of cells to vitronectin. However, pretreatment of the cells with contortrostatin or the combination of antibodies against αvβ3 and αvβ5 completely blocked adhesion to vitronectin. By contrast, either anti-αvβ5 alone or contortrostatin blocked adhesion of an αvβ3-negative T24 subline. Second, contortrostatin as well as anti-αvβ5 inhibits invasion of OVCAR-5, which express only αvβ5. Third, contortrostatin binds to purified αvβ5 in a saturable manner. Finally, radioligand binding assays yielded a Kd value of 24 nM for [125I]contortrostatin binding to αvβ5. This investigation identifies αvβ5 as a binding site for contortrostatin. Blockage of αvβ5 by contortrostatin inhibits αvβ5-mediated adhesion and invasion.