Disintegrins

Abstract

The existence of disintegrins, non-enzymatic, small molecular weight proteins from viper venom, has been known for 2 decades, and their impact on cellular research has been substantial and far-reaching. Disintegrins have been the molecular scaffold used in the design of therapeutics for the prevention of thrombosis and cancer. Their sequencing has provided insights into the evolution of proteins over millennia. Production of recombinant disintegrin mutants and fusion proteins has allowed investigations into molecular mechanisms at work in cell-extracellular matrix interactions. Structural homologies with non-snake proteins have shown disintegrin-like molecules in species ranging from slime mold to humans. Intracellular signaling events have been elucidated through the use of venom disintegrins, including events related to programmed cell death, motility, cell proliferation and viral pathogenesis. Disintegrin sequences (protein or genes) have been placed in microbubbles and liposomes and been found to target neovascular endothelium and metastatic tumors in two mouse models. The purpose of this review is to highlight the members of this disintegrin family discovered since 1998 as well as the increased understanding of their usefulness in therapeutics and technical assays.

Dynamics and functional differences between dendroaspin and rhodostomin: Insights into protein scaffolds in integrin recognition

“…12 The RGD motif is located at the apex of a long loop, between two b strands of the protein, protruding 10-17 Å from the protein core. [6][7][8][9][10][11][12] The flexibility and solvent exposure of the RGD loop are responsible for the recognition and fitting the interface between integrin a and b subunits. Studies 35,37,38 also show that the dynamic properties of the RGD motif may be important in its interaction with integrins.…”

“…The synergy between structure and dynamics is essential to the function of integrin complexes. [6][7][8][9][10][11][12] Many studies have compared the binding affinity of RGD-containing peptide with their 3D conformations and backbone dynamics. 27,36,38,43 As shown in Table IV, the residues of the RGD loop of these proteins exhibited extensive flexibility on fast motion on the picasecond per nanosecond time scale.…”

“…[3][4][5] Many toxins are obtained from a variety of species, such as snakes, ticks, and leeches, and contain an arginylglycyl-aspartic acid (RGD) motif with different protein scaffolds. [6][7][8][9][10][11] They specifically inhibit the integrin-binding function and are potent integrin antagonists. Many of these proteins have potential as therapeutic agents that can directly target integrins.…”

Purification and characterization of platelet aggregation inhibitor from the Gloydius blomhoffii brevicaudus venom

“…Дезінтегрини, що містяться в отруті Viperidae і Crоtalidae, є специфічними інгібіторами агрегації тромбоцитів, які діють як антагоністи рецептора GP IIbIIIa [29,26]. На поверхні тромбоцитів фібриноген зв'язується з інтегрином IIbIIIa, викликаючи взаємодію тромбоцит-тромбоцит, що є заключною стадією агрегації тромбоцитів, індукова-ної АДФ, тромбіном, колагеном і арахідоновою кислотою.…”

CC-PLA2-1 and CC-PLA2-2, two Cerastes cerastes venom-derived phospholipases A2, inhibit angiogenesis both in vitro and in vivo

“…5 Snake venom contains components able to disrupt cell-ECM interactions. Among these molecules, disintegrins are the most widely characterized and they are now studied for potential use in medicine (for a review, see McLane et al 6 ).…”