Three-dimensional structure of the mini-M conotoxin mr3a

Biochemistry. 2004 Jan 20;43(2):425-9. doi: 10.1021/bi0353732.

Abstract

Conotoxin mr3a from the venom of Conus marmoreus, a novel peptide that induces rolling seizures in mice, has the peptide sequence GCCGSFACRFGCVOCCV, where O is trans-4-hydroxyproline, and the chain is cross-linked with disulfide bonds between Cys-2 and Cys-16, Cys-3 and Cys-12, and Cys-8 and Cys-15. The tertiary structure of mr3a was determined by 2D 1H NMR in combination with a standard distance-geometry algorithm. The final set of 22 structures for the peptide had a mean global backbone RMS deviation of 0.53 +/- 0.22 A based on 51 NOE, 6 hydrogen bond, 6 phi dihedral angle, and 3 disulfide bond constraints. Conotoxin mr3a is the first example of the new mini-M branch of conopeptides in the M superfamily. Members of the maxi-M branch, whose structures are known, include the mu- and psi-conotoxins, both of which share a common disulfide bond connectivity. Although mr3a has the same arrangement of Cys residues as the mu- and psi-conotoxins, its disulfide connectivity is different. This gives mr3a a distinctive "triple-turn" backbone.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Computer Simulation
  • Conotoxins / chemistry*
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Mapping
  • Protein Conformation
  • Protein Folding
  • Sequence Analysis, Protein

Substances

  • Conotoxins
  • conotoxin mr3a, Conus marmoreus