I(1)-superfamily conotoxins and prediction of single D-amino acid occurrence.
The considerable diversity of Conus peptides in the I(1)-superfamily provides a rare opportunity to define parameters important for the post-translational l- to d-isomerization of amino acids. This subtlest of post-translational modifications is not readily detectable by most techniques, and it would be a considerable advance if one could predict its potential occurrence purely from gene sequences. We previously described three I(1)-conotoxins, iota-RXIA (formerly designated r11a), r11b and r11c, each containing a d-amino acid at the third position from the C-terminus. In this work, we investigated two novel I(1)-superfamily members, r11d and ar11a, which we show have only l-amino acids. Based on these observations and an analysis of cDNA sequences of other group members, we suggest that there is a rule to predict d-amino acids in I(1)-superfamily peptides. Two factors are important: the residue to be modified should be three amino acids from the C-terminus of the precursor sequence, and it should be in a suitable sequence context. We apply the rule to other members of the I(1)-superfamily, to determine a priori which are probably modified.
Buczek
Olga
O
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA. buczek@biology.utah.edu
Jimenez
Elsie C
EC
Yoshikami
Doju
D
Imperial
Julita S
JS
Watkins
Maren
M
Morrison
Alex
A
Olivera
Baldomero M
BM
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D003001:Cloning, Molecular; D020916:Conotoxins / Q000737:chemistry* / Q000494:pharmacology; D052078:Conus Snail; D018076:DNA, Complementary; D004594:Electrophysiology; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000187:drug effects; D011894:Rana pipiens; D017386:Sequence Homology, Amino Acid
D000596:Amino Acids; D020916:Conotoxins; D018076:DNA, Complementary