PDBsum entry 2fqc

Toxin

PDB id: 2fqc

Contents

Protein chain

26 a.a.

PDB id:

2fqc

Name:

Toxin

Title:

Solution structure of conotoxin pl14a

Structure:

Alpha/kappa-conotoxin pl14a. Chain: a. Synonym: conotoxin pl14a. Engineered: yes

Source:

Synthetic: yes. Conus planorbis. Planorbis cone. Organism_taxid: 97183. Other_details: chemically synthesized. This sequence occurs naturally in conus planorbis

NMR struc:

20 models

Authors:

D.J.Craik,N.L.Daly

Key ref:

J.S.Imperial et al. (2006). A novel conotoxin inhibitor of Kv1.6 channel and nAChR subtypes defines a new superfamily of conotoxins. Biochemistry, 45, 8331-8340. PubMed id: 16819832 DOI: 10.1021/bi060263r

Date:

18-Jan-06 Release date: 18-Jul-06

Protein chain

Q0N4U8  (CJEA_CONPO) -  Alpha/kappa-conotoxin pl14a from Conus planorbis

Seq: 76 a.a.

Struc: 26 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1021/bi060263r

Biochemistry 45:8331-8340 (2006)

PubMed id: 16819832

A novel conotoxin inhibitor of Kv1.6 channel and nAChR subtypes defines a new superfamily of conotoxins.

J.S.Imperial, P.S.Bansal, P.F.Alewood, N.L.Daly, D.J.Craik, A.Sporning, H.Terlau, E.López-Vera, P.K.Bandyopadhyay, B.M.Olivera.

ABSTRACT

Using assay-directed fractionation of the venom from the vermivorous cone snail Conus planorbis, we isolated a new conotoxin, designated pl14a, with potent activity at both nicotinic acetylcholine receptors and a voltage-gated potassium channel subtype. pl14a contains 25 amino acid residues with an amidated C-terminus, an elongated N-terminal tail (six residues), and two disulfide bonds (1-3, 2-4 connectivity) in a novel framework distinct from other conotoxins. The peptide was chemically synthesized, and its three-dimensional structure was demonstrated to be well-defined, with an alpha-helix and two 3(10)-helices present. Analysis of a cDNA clone encoding the prepropeptide precursor of pl14a revealed a novel signal sequence, indicating that pl14a belongs to a new gene superfamily, the J-conotoxin superfamily. Five additional peptides in the J-superfamily were identified. Intracranial injection of pl14a in mice elicited excitatory symptoms that included shaking, rapid circling, barrel rolling, and seizures. Using the oocyte heterologous expression system, pl14a was shown to inhibit both a K+ channel subtype (Kv1.6, IC50 = 1.59 microM) and neuronal (IC50 = 8.7 microM for alpha3beta4) and neuromuscular (IC50 = 0.54 microM for alpha1beta1 epsilondelta) subtypes of the nicotinic acetylcholine receptor (nAChR). Similarities in sequence and structure are apparent between the middle loop of pl14a and the second loop of a number of alpha-conotoxins. This is the first conotoxin shown to affect the activity of both voltage-gated and ligand-gated ion channels.