Identification of binding domains in the sodium channel Na(V)1.8 intracellular N-terminal region and annexin II light chain p11

• Published in: FEBS letters Vol. 558; no. 1-3; pp. 114 - 118
• Main Authors: Poon, W-Y Louisa, Malik-Hall, Misbah, Wood, John N, Okuse, Kenji
• Format: Journal Article
• Language: English
• Published: England 30.01.2004
• Subjects: Amino Acid Sequence; Animals; Annexin A2 - chemistry; Annexin A2 - genetics; Annexin A2 - metabolism; Cercopithecus aethiops; Computer Simulation; COS Cells; Dimerization; EF Hand Motifs; Glutathione Transferase - metabolism; Green Fluorescent Proteins; Luminescent Proteins - metabolism; Models, Molecular; Models, Theoretical; Protein Isoforms - chemistry; Protein Isoforms - metabolism; Protein Structure, Tertiary; Rats; Recombinant Fusion Proteins - metabolism; S100 Proteins - chemistry; S100 Proteins - genetics; S100 Proteins - metabolism; Sequence Homology, Amino Acid; Sodium Channels - chemistry; Sodium Channels - genetics; Sodium Channels - metabolism
• ISSN: 0014-5793
• DOI: 10.1016/S0014-5793(03)01512-6

The interaction of p11 (annexin II light chain) with the N-terminal domain of Na(V)1.8, a tetrodotoxin-resistant sodium channel, is essential for the functional expression of the channel. Here we show that p11 binds to Na(V)1.8 but not to sodium channel isoforms Na(V)1.2, 1.5, 1.7 or Na(V)1.9. The binding of amino acids 74-103 of Na(V)1.8 to p11 residues 33-78 occurs in a random coiled region flanked by two EF hand motifs whose crystal structure has been established. As Na(V)1.8 channel expression is associated with pain pathways, drugs that disrupt the Na(V)1.8-p11 interaction and down-regulate channel expression may have analgesic activity.