SNAKE-VENOM METALLOPROTEINASES - STRUCTURE, FUNCTION AND RELATIONSHIPTO THE ADAMS FAMILY OF PROTEINS

A large number of zinc metalloproteinases of varying mel. wts and biol ogical functions has been isolated from crotalid and viperid venoms. O ver the past few years, structural studies on these proteinases have s uggested their organization into four classes, P-I to P-IV. These prot einases are synthesized in the venom gland as zymogens which are subse quently processed to the active form. The signal and pro-sequences of the proteins are highly conserved. Within the pro-domain lies a consen sus sequence which probably functions in a manner similar to the cyste ine switch in mammalian collagenases. The proteinase domain is represe nted by two forms: a two-disulfide and a three-disulfide structure. Cr ystallographic and modeling studies suggest that the two forms share v ery similar tertiary structures. The larger venom metalloproteinases ( P-II, III and IV) have additional domains on the carboxy side of the p roteinase domain. The additional domains that have been identified inc lude disintegrin and disintegrin-like domains, a high-cysteine domain and a lectin-binding domain. It appears that these non-enzymatic domai ns function to modulate the biological properties of the proteinases. Recently, a family of homologues of the venom zinc metalloproteinases has been described from a variety of organisms including mammals, rept iles and invertebrates. This family of proteins has been termed the AD AMs, for A Disintegrin-like And Metalloproteinase-containing protein. They differ from the venom proteinases in that some of them may not ha ve proteolytic activity. In addition to the domain structure described for the P-III class of venom proteins, the ADAMs have an epidermal gr owth factor-like domain, a transmembrane domain and a cytoplasmic doma in. A description of venom metalloproteinase structure will be outline d in this review, along with the similarities and differences among th e venom proteins and the ADAMs family of proteins. Copyright (C) 1996 Elsevier Science Ltd