3SQ9

Crystal Structures of the Ligand Binding Domain of a Pentameric Alpha7 Nicotinic Receptor Chimera

3SQ9 の概要

• エントリーDOI: 10.2210/pdb3sq9/pdb
• 関連するPDBエントリー: 3SQ6
• 分子名称: 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, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: nicotinic receptor, transport protein-receptor complex, transport protein/receptor
• 由来する生物種: Homo sapiens, Lymnaea stagnalis (human, great pond snail)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 240778.01

構造登録者

Li, S.-X.,Huang, S.,Bren, N.,Noridomi, K.,Dellisanti, C.,Sine, S.,Chen, L. (登録日: 2011-07-05, 公開日: 2011-09-28, 最終更新日: 2024-10-09)

主引用文献

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

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: 21909087
DOI: 10.1038/nn.2908

実験手法

X-RAY DIFFRACTION (3.1 Å)