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Acetylcholine binding protein (AChBP) is a homolog of the ligand-binding domain of the nicotinic acetylcholine receptor (nAChR). We have solved the crystal structure of AChBP (Brejc et al., Nature, 2001) and found that it modulates synaptic tranmission
in the central nervous system of the snail Lymnaea stagnalis (Smit
et al., Nature, 2001). The ligand binding site is formed at the interface between subunits and is composed of highly conserved aromatic residues, which form an electronic-rich cage around the ligand (Celie
et al., Neuron, 2004).
Co-crystal structures of AChBPs from different snails (Celie
et al., JBC, 2005) in complex with alpha-conotoxins has given insight in the conformational changes that occur upon agonist- and antagonist-binding and the structural determinants for subtype-selective binding to different AChBPs and nAChRs (Celie
et al., NSMB, 2005 & Ulens
et al., PNAS, 2006).
Our crystal structures serve as a structural template to design new ligands to treat nAChR-related disorders such as Alzheimer's and Parkinson's disease, schizophrenia and smoking addiction.
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