2BR8: Crystal Structure Of Acetylcholine-Binding Protein (Achbp) From Aplysia Californica In Complex With An Alpha- Conotoxin Pnia Variant

Citation:
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.
PDB ID: 2BR8Download
MMDB ID: 86833
PDB Deposition Date: 2005/5/3
Updated in MMDB: 2010/12
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Conus pennaceus
Similar Structures:
Biological Unit for 2BR8: decameric; determined by author and by software (PQS)
Molecular Components in 2BR8
Label Count Molecule
Proteins (10 molecules)
5
Soluble Acetylcholine Receptor
Molecule annotation
5
Alpha-conotoxin Pnia
Molecule annotation
Chemicals (5 molecules)
1
5
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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