5HCM

The GLIC pentameric Ligand-Gated Ion Channel 2-21' cross-linked mutant complexed to bromoform

5HCM の概要

• エントリーDOI: 10.2210/pdb5hcm/pdb
• 分子名称: Proton-gated ion channel, DODECYL-BETA-D-MALTOSIDE, TRIBROMOMETHANE (3 entities in total)
• 機能のキーワード: ion channel, receptor, anaesthetic, transport protein
• 由来する生物種: Gloeobacter violaceus
• 細胞内の位置: Cell inner membrane ; Multi- pass membrane protein : Q7NDN8
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 181956.79

構造登録者

Shahsavar, A.,Sauguet, L.,Delarue, M. (登録日: 2016-01-04, 公開日: 2016-04-13, 最終更新日: 2024-10-23)

主引用文献

Laurent, B.,Murail, S.,Shahsavar, A.,Sauguet, L.,Delarue, M.,Baaden, M.
Sites of Anesthetic Inhibitory Action on a Cationic Ligand-Gated Ion Channel.
Structure, 24:595-605, 2016

PubMed Abstract: Pentameric ligand-gated ion channels have been identified as the principal target of general anesthetics (GA), whose molecular mechanism of action remains poorly understood. Bacterial homologs, such as the Gloeobacter violaceus receptor (GLIC), have been shown to be valid functional models of GA action. The GA bromoform inhibits GLIC at submillimolar concentration. We characterize bromoform binding by crystallography and molecular dynamics (MD) simulations. GLIC's open form structure identified three intra-subunit binding sites. We crystallized the locally closed form with an additional bromoform molecule in the channel pore. We systematically compare binding with the multiple potential sites of allosteric channel regulation in the open, locally closed, and resting forms. MD simulations reveal differential exchange pathways between sites from one form to the other. GAs predominantly access the receptor from the lipid bilayer in all cases. Differential binding affinity among the channel forms is observed; the pore site markedly stabilizes the inactive versus active state.

PubMed: 27021161
DOI: 10.1016/j.str.2016.02.014

実験手法

X-RAY DIFFRACTION (3.15 Å)