2br8: Difference between revisions

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.

[[Category: Celie, P H.N.]]

[[Category: Elk, R Van.]]

[[Category: Hogg, R C.]]

[[Category: Kasheverov, I E.]]

[[Category: Mordvintsev, D Y.]]

[[Category: Nierop, P Van.]]

[[Category: Rossum-Fikkert, S E.Van.]]

[[Category: Sixma, T K.]]

[[Category: Smit, A B.]]

[[Category: Zhmak, M N.]]

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