Identification of binding domains in the sodium channel Na(V)1.8 intracellular N-terminal region and annexin II light chain p11.
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.
Poon
W-Y Louisa
WY
Department of Biology, University College London, Gower Street, London WC1E 6BT, UK.
Malik-Hall
Misbah
M
Wood
John N
JN
Okuse
Kenji
K
D000595:Amino Acid Sequence; D000818:Animals; D017306:Annexin A2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003198:Computer Simulation; D019281:Dimerization; D020832:EF Hand Motifs; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D008958:Models, Molecular; D008962:Models, Theoretical; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D009418:S100 Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D005982:Glutathione Transferase; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D009418:S100 Proteins; D015222:Sodium Channels; D000099248:S100 Calcium Binding Protein A10