The complex array of bradykinin-related peptides (BRPs) in the peptidome of pickerel frog (Rana palustris) skin secretion is the product of transcriptional economy.
Previous peptidomic analyses of the defensive skin secretion from the North American pickerel frog, Rana palustris, have established the presence of canonical bradykinin and multiple bradykinin-related peptides (BRPs). As a consequence of the multiplicity of peptides identified and their diverse primary structures, it was speculated that they must represent the products of expression of multiple genes. Here, we present unequivocal evidence that the majority of BRPs (11/13) identified in skin secretion by the peptidomic approach can be generated by differential site-specific protease cleavage from a single common precursor of 321 amino acid residues, named skin kininogen 1, whose primary structure was deduced from cloned skin secretion-derived cDNA. The organization of skin kininogen 1 consists of a hydrophobic signal peptide followed by eight non-identical domains each encoding a single copy of either canonical bradykinin or a BRP. Two additional splice variants, encoding precursors of 233 (skin kininogen 2) or 189 amino acid residues (skin kininogen 3), were also cloned and were found to lack BRP-encoding domains 5 and 6 or 4, 5 and 6, respectively. Thus, generation of peptidome diversity in amphibian defensive skin secretions can be achieved in part by differential protease cleavage of relatively large and multiple-encoding domain precursors reflecting a high degree of transcriptional economy.
McCrudden
Cian Michael
CM
Molecular Therapeutics Research, School of Pharmacy, Medical Biology Center, Queen's University, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
Zhou
Mei
M
Chen
Tianbao
T
O'Rourke
Martin
M
Walker
Brian
B
Hirst
David
D
Shaw
Chris
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D012634:Bodily Secretions / Q000737:chemistry*; D001920:Bradykinin / Q000737:chemistry / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D007704:Kininogens / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000235:genetics; D011898:Ranidae / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D014158:Transcription, Genetic
D018076:DNA, Complementary; D007704:Kininogens; D010455:Peptides; D021382:Protein Sorting Signals; D020543:Proteome; D001920:Bradykinin