3SQ6
Crystal Structures of the Ligand Binding Domain of a Pentameric Alpha7 Nicotinic Receptor Chimera with its Agonist Epibatidine
Summary for 3SQ6
| Entry DOI | 10.2210/pdb3sq6/pdb |
| Related | 3SQ9 |
| Descriptor | Neuronal acetylcholine receptor subunit alpha-7, Acetylcholine-binding protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, EPIBATIDINE, ... (5 entities in total) |
| Functional Keywords | nicotinic receptor, transport protein-receptor-agonist complex, transport protein/receptor/agonist |
| Biological source | Homo sapiens, Lymnaea stagnalis (human, great pond snail) |
| Total number of polymer chains | 10 |
| Total formula weight | 241794.87 |
| Authors | Li, S.-X.,Huang, S.,Bren, N.,Noridomi, K.,Dellisanti, C.,Sine, S.,Chen, L. (deposition date: 2011-07-05, release date: 2011-09-28, Last modification date: 2024-10-09) |
| Primary citation | Li, S.X.,Huang, S.,Bren, N.,Noridomi, K.,Dellisanti, C.D.,Sine, S.M.,Chen, L. Ligand-binding domain of an alpha 7-nicotinic receptor chimera and its complex with agonist. Nat.Neurosci., 14:1253-1259, 2011 Cited by PubMed Abstract: The α(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 α(7) AChR and Lymnaea stagnalis acetylcholine binding protein (AChBP), which shares 64% sequence identity and 71% similarity with native α(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 α(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 α(7) AChRs. The structures provide a realistic template for structure-aided drug design and for defining structure-function relationships of α(7) AChRs. PubMed: 21909087DOI: 10.1038/nn.2908 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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