PDBsum entry 2yyf

Toxin

PDB id: 2yyf

Contents

Protein chain

15 a.a.

References listed in PDB file

Key reference

• Title: Purification and structural characterization of a d-Amino acid-Containing conopeptide, Conomarphin, From conus marmoreus.
• Authors: Y.Han, F.Huang, H.Jiang, L.Liu, Q.Wang, Y.Wang, X.Shao, C.Chi, W.Du, C.Wang.
• Ref.: Febs J, 2008, 275, 1976-1987.
• PubMed id: 18355315

Abstract

Cone snails, a group of gastropod animals that inhabit tropical seas, are capable of producing a mixture of peptide neurotoxins, namely conotoxins, for defense and predation. Conotoxins are mainly disulfide-rich short peptides that act on different ion channels, neurotransmitter receptors, or transporters in the nervous system. They exhibit highly diverse compositions, structures, and biological functions. In this work, a novel Cys-free 15-residue conopeptide from Conus marmoreus was purified and designated as conomarphin. Conomarphin is unique because of its D-configuration Phe at the third residue from the C-terminus, which was identified using HPLC by comparing native conomarphin fragments and the corresponding synthetic peptides cleaved by different proteases. Surprisingly, the cDNA-encoded precursor of conomarphin was found to share the conserved signal peptide with other M-superfamily conotoxins, clearly indicating that conomarphin should belong to the M-superfamily, although conomarphin shares no homology with other six-Cys-containing M-superfamily conotoxins. Furthermore, NMR spectroscopy experiments established that conomarphin adopts a well-defined structure in solution, with a tight loop in the middle of the peptide and a short 3(10)-helix at the C-terminus. By contrast, no loop in L-Phe13-conomarphin was found, which suggests that D-Phe13 is essential for the structure of conomarphin. In conclusion, conomarphin may represent a new conotoxin family, whose biological activity remains to be identified.