The M-superfamily, one of eight major conotoxin superfamilies found in the venom of the cone snail, contains a Cys framework with disulfide-linked loops labeled 1, 2, and 3 (- CC1C2C3CC-). M-superfamily conotoxins can be divided into the m-1, -2, -3 and -4 branches, based upon the number of residues located in the third Cys loop between the fourth and fifth Cys residues. Here we provide a three-dimensional solution structure for the m-1 conotoxin tx3a found in the venom of Conus textile. The 15 amino acid peptide, CCSWDVCDHPSCTCC, has disulfide bonds between Cys1 and Cys14, Cys2 and Cys12, and Cys7 and Cys15 typical of the C1- C5, C2-C4, and C3-C6 connectivity pattern seen in m-1 branch peptides. The tertiary structure of tx3a was determined by 2D 1H NMR in combination with the combined assignment and dynamics algorithm for nuclear magnetic resonance (NMR) applications CYANA program. Input for structure calculations consisted of 62 inter- and intraproton, 5 phi angle, and 4 hydrogen bond constraints. The root-mean-square deviation values for the 20 final structures are 0.32 +/- 0.07 Å and 0.84 +/- 0.11 Å for the backbone and heavy atoms, respectively. Surprisingly, the structure of tx3a has a “triple-turn” motif seen in the m-2 branch conotoxin mr3a, which is absent in mr3e, the only other member of the m-1 branch of the M-superfamily whose structure is known. Interestingly, injection of tx3a into mice elicits an excitatory response similar to that of the m-2 branch peptide mr3a, even though the conotoxins have different disulfide connectivity patterns.
This document is the unedited author's version of a submitted work that was subsequently accepted for publication in Biochemistry, ©2008 American Chemical Society after peer review. To access the final edited and published work see: DOI 10.1021/bi702388b
McDougal, Owen M.; Turner, Matthew W.; Ormond, Andrew J.; and Poulter, C. Dale. (2008). "Three-Dimensional Structure of Conotoxin tx3a: A m-1 Branch Peptide of the M-Superfamily". Biochemistry, 47(9), 2826-2832.