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Identification of a cluster of residues in transmembrane segment 6 of domain III of the cockroach sodium channel essential for the action of pyrethroid insecticides.

Publication ,  Journal Article
Du, Y; Lee, J-E; Nomura, Y; Zhang, T; Zhorov, BS; Dong, K
Published in: The Biochemical journal
April 2009

A phenylalanine residue (Phe1519) in the sixth transmembrane segment of domain III (IIIS6) of the cockroach BgNa(v) sodium channel is required for the binding and action of pyrethroids. However, whether or not other residues in IIIS6 participate in the action of pyrethroids remains to be determined. In the present study, we conducted a systematic analysis of 20 residues in IIIS6 of the BgNa(v) channel using alanine-scanning mutagenesis. Our results show that alanine substitutions of four residues, Ile1514, Gly1516, Phe1518 and Asn1522, altered sodium channel sensitivity to pyrethroid insecticides. Whereas the G1516A, F1518A and N1522A substitutions diminished sodium channel sensitivity to all seven pyrethroids examined, including four type I (lacking the alpha-cyano group at the phenoxybenzyl alcohol) and three type II (containing the alpha-cyano group) pyrethroids, the I1514A substitution enhanced sodium channel sensitivity to four type I and type II pyrethroids that contain the phenoxybenzyl alcohol only. We also show that alanine/lysine substitutions of Leu1521 and Ser1517 affected the action of BTX (batrachotoxin), but not pyrethroids. In the Kv1.2-based homology model of the open sodium channel, side chains of Ile1514, Phe1518 and Asn1522 are exposed towards helix IIS5 and linker IIS4-IIS5, which contain previously identified pyrethroid-interacting residues, whereas Ser1517 and Leu1521 face the inner pore where the BTX receptor is located. Thus the present study provides further evidence for structural models in which pyrethroids bind to the lipid-exposed interface formed by helices IIIS6, IIS5 and linker helix IIS4-IIS5, whereas BTX binds to the pore-exposed side of the IIIS6 helix.

Duke Scholars

Published In

The Biochemical journal

DOI

EISSN

1470-8728

ISSN

0264-6021

Publication Date

April 2009

Volume

419

Issue

2

Start / End Page

377 / 385

Related Subject Headings

  • Sodium Channels
  • Pyrethrins
  • Protein Structure, Tertiary
  • Protein Binding
  • Mutagenesis, Site-Directed
  • Insecticides
  • Insect Proteins
  • Electrophysiology
  • Cockroaches
  • Biochemistry & Molecular Biology
 

Citation

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Du, Y., Lee, J.-E., Nomura, Y., Zhang, T., Zhorov, B. S., & Dong, K. (2009). Identification of a cluster of residues in transmembrane segment 6 of domain III of the cockroach sodium channel essential for the action of pyrethroid insecticides. The Biochemical Journal, 419(2), 377–385. https://doi.org/10.1042/bj20082082
Du, Yuzhe, Jung-Eun Lee, Yoshiko Nomura, Tianxiang Zhang, Boris S. Zhorov, and Ke Dong. “Identification of a cluster of residues in transmembrane segment 6 of domain III of the cockroach sodium channel essential for the action of pyrethroid insecticides.The Biochemical Journal 419, no. 2 (April 2009): 377–85. https://doi.org/10.1042/bj20082082.
Du, Yuzhe, et al. “Identification of a cluster of residues in transmembrane segment 6 of domain III of the cockroach sodium channel essential for the action of pyrethroid insecticides.The Biochemical Journal, vol. 419, no. 2, Apr. 2009, pp. 377–85. Epmc, doi:10.1042/bj20082082.

Published In

The Biochemical journal

DOI

EISSN

1470-8728

ISSN

0264-6021

Publication Date

April 2009

Volume

419

Issue

2

Start / End Page

377 / 385

Related Subject Headings

  • Sodium Channels
  • Pyrethrins
  • Protein Structure, Tertiary
  • Protein Binding
  • Mutagenesis, Site-Directed
  • Insecticides
  • Insect Proteins
  • Electrophysiology
  • Cockroaches
  • Biochemistry & Molecular Biology