title: Solution structure of Lqh-8/6, a toxin-like peptide from a scorpion venom--structural heterogeneity induced by proline cis/trans isomerization.
abstract: Lqh-8/6 is a minor fraction isolated from the venom of the scorpion Leiurus quinquestriatus hebraeus. Here we describe the purification, amino acid sequencing and solution structure determination by NMR and molecular modeling of this peptide. Lqh-8/6 is a small polypeptide (38 residues) which contains 8 half-cystines and is highly similar to another venom component, chlorotoxin. Standard homonuclear methods were used to sequentially assign the proton NMR spectra and to collect spatial restraints for structure determination. Two populations, identified early in the assignment step, are in slow interconversion on the NMR timescale. The two conformers were shown to originate from a cis/trans peptidyl-prolyl isomerization. Using a distance geometry program and simulated annealing protocol under the NMR restraints we obtained 10 final structures for the major conformation (trans isomer). None of the structures showed NOE violations larger than 0.05 nm, and the rmsd value relative to the mean structure (considering the main chain atoms in well-defined secondary structure) is 0.07 nm. The three-dimensional structure contains a short alpha-helix strapped on a small antiparallel beta-strand and an N-terminal extended fragment. The sequence/structure and structure/function relationships of the new scorpion toxin-like peptide are discussed in the context of the present structure determination. This toxin shows a stable, highly populated cis conformer of a peptidyl-prolyl peptide bond.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U350 and Institut Curie, Orsay, France.
authors.forename: E
authors.initials: E
authors.lastname: Adjadj
authors.forename: V
authors.initials: V
authors.lastname: Naudat
authors.forename: E
authors.initials: E
authors.lastname: Quiniou
authors.forename: D
authors.initials: D
authors.lastname: Wouters
authors.forename: P
authors.initials: P
authors.lastname: Sautière
authors.forename: C T
authors.initials: CT
authors.lastname: Craescu
mesh_terms: D000595:Amino Acid Sequence; D019476:Insect Proteins; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012604:Scorpion Venoms / Q000737:chemistry* / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D019476:Insect Proteins; C106962:Lqh 8-6 protein, Leiurus quinquestriatus hebraeus; D009498:Neurotoxins; D012604:Scorpion Venoms; C091539:Chlorotoxin; D011392:Proline