PDBsum entry 1lmm

Toxin

PDB id: 1lmm

Contents

Protein chain

40 a.a.

PDB id:

1lmm

Name:

Toxin

Title:

Solution structure of psmalmotoxin 1, the first characterized specific blocker of asic1a na+ channel

Structure:

Psalmotoxin 1. Chain: a. Synonym: pctx1. Engineered: yes

Source:

Psalmopoeus cambridgei. Trinidad chevron tarantula. Organism_taxid: 179874. Expressed in: escherichia coli. Expression_system_taxid: 562

NMR struc:

20 models

Authors:

P.Escoubas,C.Bernard,M.Lazdunski,H.Darbon

Key ref:

P.Escoubas et al. (2003). Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels. Protein Sci, 12, 1332-1343. PubMed id: 12824480 DOI: 10.1110/ps.0307003

Date:

02-May-02 Release date: 25-Nov-03

Protein chain

P60514  (TXP1_PSACA) -  Psalmotoxin-1 from Psalmopoeus cambridgei

Seq: 40 a.a.

Struc: 40 a.a.

DOI no: 10.1110/ps.0307003

Protein Sci 12:1332-1343 (2003)

PubMed id: 12824480

Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels.

P.Escoubas, C.Bernard, G.Lambeau, M.Lazdunski, H.Darbon.

ABSTRACT

Acid-sensing ion channels (ASICs) are thought to be important ion channels, particularly for the perception of pain. Some of them may also contribute to synaptic plasticity, learning, and memory. Psalmotoxin 1 (PcTx1), the first potent and specific blocker of the ASIC1a proton-sensing channel, has been successfully expressed in the Drosophila melanogaster S2 cell recombinant expression system used here for the first time to produce a spider toxin. The recombinant toxin was identical in all respects to the native peptide, and its three-dimensional structure in solution was determined by means of (1)H 2D NMR spectroscopy. Surface characteristics of PcTx1 provide insights on key structural elements involved in the binding of PcTx1 to ASIC1a channels. They appear to be localized in the beta-sheet and the beta-turn linking the strands, as indicated by electrostatic anisotropy calculations, surface charge distribution, and the presence of residues known to be implicated in channel recognition by other inhibitor cystine knot (ICK) toxins.

Selected figure(s)

Figure 4.
Figure 4. (A) Stereoview of the best fit of 20 solution structures of PcTx1. C[ ]are shown. The N and C termini are labeled "N" and "C". (B) Molecular surface colored according to the electrostatic charge (red for acidic and blue for basic) and the resulting dipolar moment (red arrow). The aromatic residues are indicated and colored in purple. (C) CPK representation of the proposed functional surface of PcTx1. The residues suspected to be important for the interaction of the toxin with the channel are labeled. Residues are colored as follows: green for polar uncharged residues, blue for basic residues, red for acidic residues, purple for aromatic residues, and yellow for aliphatic residues.

Figure 6.
Figure 6. Comparison of putative functional dyads of PcTx1 (A) and related ICK toxins J-atracotoxin Hv1c (PDB 1DL0 [PDB] ; B), -conotoxin PVIIA (PDB 1KCP [PDB] ; C), and agitoxin 2 (PDB 1AGT [PDB] ; D). Basic residues side chains are colored in blue; aromatic residues side chains, in orange.

The above figures are reprinted by permission from the Protein Society: Protein Sci (2003, 12, 1332-1343) copyright 2003.

Figures were selected by an automated process.