Non-RGD-containing snake venom disintegrins, functional and structural relations

Snake venom disintegrins are present in a variety of species and are functionally divided into three families: RGD, MLD and R/KTS. The RGD family of disintegrins, which bind and inhibit the physiological functions of RGD-dependent integrins, constitute the largest and most investigated family. This review will be focused on characterization of two relatively new families of snake venom disintegrins, expressing in their active site MLD and R/KTS motifs. The MLD motif, present only in heterodimeric disintegrins, mediates binding of these disintegrins to α4β1, α4β7 and α9β1 integrins, whereas the presence of a KTS or RTS sequence in the active site selectively directs activity of disintegrins to the collagen receptor α1β1 integrin. Structurally, KTS-disintegrins are short, monomeric molecules containing 41 amino acids in its polypeptide chain. Biological activities of MLD and KTS-disintegrins were investigated in many systems in vitro and in vivo. Purified disintegrins are non-toxic in therapeutic doses in rodent and avian models. Their modulatory properties were observed in investigations of cancer angiogenesis and metastasis, immunosuppression of IDDM (insulin-dependent diabetes mellitus) and asthma, as well as in neurodegenerative assays and cell apoptosis.