A novel strategy for the identification of toxinlike structures in spider venom.
We compared two different approaches to sequence information analysis from the expressed sequence tag (EST) library constructed for the venom glands of the spider Agelena orientalis. Some results were more illustrative and reliable by the contig analysis technique, whereas our novel method, with specific structural markers introduced for protein structure detection, allowed us to overcome some limitations of the contig analysis. A novel technique was suggested for the identification in data banks of the spider's ion channel inhibitor toxins using primary structure features common to all spiders. Analysis of about 150 polypeptides made it possible to introduce 3 primary structure motifs for spider toxins: the Principal Structural Motif (PSM), which postulates the existence of 6 amino acid residues between the first and second cysteine residue and the Cys-Cys sequence at a distance of 5-10 amino acid residues from the second cysteine; the Extra Structural Motif (ESM), which postulates the existence of a pair of CXC fragments in the C-region; and the Processing Quadruplet Motif (PQM), which specifies the Arg residue at position -1 and Glu residues at positions -2, -3, and/or -4 in the precursor sequences just before the postprocessing site. In the processed data bank we found 48 toxinlike structures with ion channel inhibitor motifs. These include agelenin earlier isolated from Agelena opulenta and 25 more homologous sequences, 15 homologs of mu-agatoxin 2 from the spider Agelenopsis aperta, 3 structures with low homology to omega-agatoxin-IIIA, and 4 new structures. Also we showed that toxinlike structures exceed two thirds of the overall database sequences.
Kozlov
Sergey
S
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. serg@ibch.ru <serg@ibch.ru>
Malyavka
Anton
A
McCutchen
Bill
B
Lu
Albert
A
Schepers
Eric
E
Herrmann
Rafi
R
Grishin
Eugene
E
D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D004261:DNA Replication; D018076:DNA, Complementary; D020224:Expressed Sequence Tags; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D013111:Spider Venoms / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D013112:Spiders
D018076:DNA, Complementary; D010455:Peptides; D011994:Recombinant Proteins; D013111:Spider Venoms