Taylor_2000_Pflugers.Arch_440_R115

Reference

Title : Subunit interface selective toxins as probes of nicotinic acetylcholine receptor structure - Taylor_2000_Pflugers.Arch_440_R115
Author(s) : Taylor P , Malanz S , Molles BE , Osaka H , Tsigelny I
Ref : Pflugers Arch , 440 :R115 , 2000
Abstract :

The pentametric assembly of the nicotinic acetylcholine receptor with two of the five subunit interfaces serving as a ligand binding sites offers an opportunity to distinguish features on the surfaces of the subunits, and their ligand specificity characteristics. The receptor from mammalian muscle, with its circular order of homologous subunits (alphagamma alphadelta beta), assembles in a unique arrangement. The residues governing assembly can be ascertained through mutagenesis. Selectivity of certain natural toxins is sufficient to distinguish between sites at the alphagamma and alphadelta subunit interfaces. By interchanging residues on the gamma and delta subunits through mutagenesis, and ascertaining how they interact with the alpha subunit, determinants forming the binding sites can be delineated. The alpha-conotoxins show a 10,000-fold preference for the alphadelta over alphagamma subunit interface with alphaepsilon falling in between. The waglerins show a 2,000-fold preference for alphaepsilon over the alphagamma and alphadelta interfaces. Finally, the alpha-neurotoxin from N. mossambica mossambica shows a 10,000-fold preference for the alphagamma and alphadelta interfaces over alphaepsilon. Identification of interactive residues through mutagenesis, when coupled with homology modeling of domains and site-directed residue modification, has revealed important elements of receptor structure.

PubMedSearch : Taylor_2000_Pflugers.Arch_440_R115
PubMedID: 11005635

Related information

Citations formats

Taylor P, Malanz S, Molles BE, Osaka H, Tsigelny I (2000)
Subunit interface selective toxins as probes of nicotinic acetylcholine receptor structure
Pflugers Arch 440 :R115

Taylor P, Malanz S, Molles BE, Osaka H, Tsigelny I (2000)
Pflugers Arch 440 :R115