Structural highlights
Publication Abstract from PubMed
The alpha(7) acetylcholine receptor (AChR) mediates pre- and postsynaptic neurotransmission in the central nervous system and is a potential therapeutic target in neurodegenerative, neuropsychiatric and inflammatory disorders. We determined the crystal structure of the extracellular domain of a receptor chimera constructed from the human alpha(7) AChR and Lymnaea stagnalis acetylcholine binding protein (AChBP), which shares 64% sequence identity and 71% similarity with native alpha(7). We also determined the structure with bound epibatidine, a potent AChR agonist. Comparison of the structures revealed molecular rearrangements and interactions that mediate agonist recognition and early steps in signal transduction in alpha(7) AChRs. The structures further revealed a ring of negative charge within the central vestibule, poised to contribute to cation selectivity. Structure-guided mutational studies disclosed distinctive contributions to agonist recognition and signal transduction in alpha(7) AChRs. The structures provide a realistic template for structure-aided drug design and for defining structure-function relationships of alpha(7) AChRs.
Ligand-binding domain of an alpha7-nicotinic receptor chimera and its complex with agonist.,Li SX, Huang S, Bren N, Noridomi K, Dellisanti CD, Sine SM, Chen L Nat Neurosci. 2011 Sep 11;14(10):1253-9. doi: 10.1038/nn.2908. PMID:21909087[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li SX, Huang S, Bren N, Noridomi K, Dellisanti CD, Sine SM, Chen L. Ligand-binding domain of an alpha7-nicotinic receptor chimera and its complex with agonist. Nat Neurosci. 2011 Sep 11;14(10):1253-9. doi: 10.1038/nn.2908. PMID:21909087 doi:https://dx.doi.org/10.1038/nn.2908
