Bradykinin-potentiating peptides and C-type natriuretic peptides from snake venom

Cloning of cDNAs encoding bradykinin-potentiating peptides (BPPs)-C-type na triuretic peptide (CNP) precursor or its homologue was performed for cDNA l ibraries of Bothrops jararaca (South American snake), Trimeresurus flavovir idis, Trimeresurus gramineus and Agkistrodon halys blomhoffi (Asian snakes) , all belonging to Crotalinae subfamily. Each cDNA library was constructed from the venom glands of a single snake to preclude ambiguity by intraspeci es variation in venom components. Thirteen positive clones derived from B. jararaca were divided into two types depending on restriction sites. Differ ences in the nucleotide sequence arise at three locations and two of them a ccompanied amino acid conversions. Despite the differences, both types of c DNA clones encode the BPP-CNP precursor of 256 amino acid residues. Sequenc e analysis demonstrated that cDNA clones from three Asian snakes encode hom ologues of the BPP-CNP precursor from B. jararaca. In a precursor polypepti de, a signal sequence (similar to 25 aa) at the N-terminus is followed by s equences of BPP or the analogue (5-13 aa) with flanking spacer sequences (i ndefinite number of aa), an intervening linker sequence (similar to 144 aa) with unidentified function, and a CNP sequence (22 aa) with a preceding pr ocessing signal sequence (10 aa), cDNA clones from A. halys blomhoffi encod e two distinct peptides in place of BPP, and T. flavoviridis and T, gramine us were shown to have considerably different sequences in the BPP domain fr om those known as BPP sequences. The present results provide evidence for a wide distribution of the orthologous gene expressing a series of bioactive peptides among Crotalinae subfamily. (C) 1999 Elsevier Science B.V. All ni ghts reserved.