Download MendeleyCrystal Structure of Nicotinic Acetylcholine Receptor Homolog Achbp in Complex with an Alpha- Conotoxin Pnia Variant
Celie, P.H.N., Kasheverov, I.E., Mordvintsev, D.Y., Hogg, R.C., Van Nierop, P., Van Elk, R., Van Rossum-Fikkert, S.E., Zhmak, M.N., Bertrand, D., Tsetlin, V., Sixma, T.K., Smit, A.B.(2005) Nat Struct Mol Biol 12: 582
- PubMed: 15951818
- DOI: https://doi.org/10.1038/nsmb951
- Primary Citation of Related Structures:
2BR7, 2BR8 - PubMed Abstract:
Conotoxins (Ctx) form a large family of peptide toxins from cone snail venoms that act on a broad spectrum of ion channels and receptors. The subgroup alpha-Ctx specifically and selectively binds to subtypes of nicotinic acetylcholine receptors (nAChRs), which are targets for treatment of several neurological disorders. Here we present the structure at a resolution of 2.4 A of alpha-Ctx PnIA (A10L D14K), a potent blocker of the alpha(7)-nAChR, bound with high affinity to acetylcholine binding protein (AChBP), the prototype for the ligand-binding domains of the nAChR superfamily. Alpha-Ctx is buried deep within the ligand-binding site and interacts with residues on both faces of adjacent subunits. The toxin itself does not change conformation, but displaces the C loop of AChBP and induces a rigid-body subunit movement. Knowledge of these contacts could facilitate the rational design of drug leads using the Ctx framework and may lead to compounds with increased receptor subtype selectivity.
- Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Organizational Affiliation:
