The scorpine family of defensins: gene structure, alternative polyadenylation and fold recognition.
Small cationic antimicrobial peptides (SCAMPs) as effectors of animal innate immunity provide the first defense against infectious pathogens. This class of molecules exists widely in invertebrate hemolymph and vertebrate skin secretion, but animal venoms are emerging as a new rich resource. Scorpine is a unique scorpion venom defensin peptide that has an extended amino-terminal sequence similar to cecropins. From the African scorpion Opistophthalmus carinatus venom gland, we isolated and identified several cDNAs encoding four new homologs of scorpine (named opiscorpines 1-4). Importantly, we show for the first time the existence of multiple opiscorpine mRNAs with variable 3' untranslated regions (UTRs) in the venom gland, which may be generated by alternative usage of polyadenylation signals. The complete opiscorpine gene structure including its promoter region is determined by genomic DNA amplification. Two large introns were found to be located within the 5' UTR and at the boundary of the mature peptide-coding region. Such a gene structure is distinct, when compared with other scorpion venom peptide genes. However, a comparative promoter analysis revealed that both opiscorpine and scorpion venom neurotoxins share a similar promoter organization. Sequence analysis and structural modeling allow us to group the scorpines and scorpion long-chain K-channel toxins together into one family that shares a similar fold with two distinct domains. The N-terminal cecropin-like domain displaying a clear antimicrobial activity implies that the scorpine family represents a group of real naturally occurring hybrids. Based on the phylogenetic analysis, a possible cooperative interaction between the N and C domains is elucidated, which provides an evolutionary basis for the design of a new class of anti-infectious drugs.
Zhu
S
S
Laboratory of Toxicology, University of Leuven, E. Van Evenstraat 4, 3000, Belgium.
Tytgat
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D023082:Defensins / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D026723:Polyadenylation / Q000502:physiology*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012605:Scorpions; D017422:Sequence Analysis, DNA
D023082:Defensins; D011506:Proteins; D012333:RNA, Messenger; C407873:scorpine