Contortrostatin, a homodimeric disintegrin, binds to integrin alphavbeta5.

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Contortrostatin is a homodimeric disintegrin found in snake venom.
• Previous studies indicated contortrostatin binds to integrins alphaIIbbeta3, alpha5beta1, and alphavbeta3.

Purpose of the Study:

• To investigate and confirm the binding of contortrostatin to the integrin alphavbeta5.
• To elucidate the functional consequences of contortrostatin binding to alphavbeta5.

Main Methods:

• Cell adhesion assays using T24 cells and a T24 subline with vitronectin.
• Invasion assays with OVCAR-5 cells.
• Saturation binding assays with purified alphavbeta5.
• Radioligand binding assays to determine the dissociation constant (Kd).

Main Results:

• Contortrostatin, alone or with specific antibodies, blocked T24 cell adhesion to vitronectin, indicating interaction with alphavbeta5.
• Contortrostatin inhibited invasion of OVCAR-5 cells, which express alphavbeta5.
• Binding of contortrostatin to purified alphavbeta5 was saturable.
• Radioligand assays determined a Kd of 24 nM for [(125)I]contortrostatin binding to alphavbeta5.

Conclusions:

• This study identifies alphavbeta5 as a direct binding site for contortrostatin.
• Contortrostatin effectively inhibits alphavbeta5-mediated cell adhesion and invasion.
• Alphavbeta5 represents a potential therapeutic target for contortrostatin-based interventions.