9BWC

Homomeric alpha3 glycine receptor in the presence of 0.1 mM glycine at pH 6.4 in an apo state

9BWC の概要

• エントリーDOI: 10.2210/pdb9bwc/pdb
• EMDBエントリー: 44964
• 分子名称: Glycine receptor subunit alpha-3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (6 entities in total)
• 機能のキーワード: glycine, ion channel, ligand-gated, pentameric, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 301109.00

構造登録者

Kindig, K.,Gibbs, E.,Chakrapani, S. (登録日: 2024-05-21, 公開日: 2024-11-13, 最終更新日: 2025-05-28)

主引用文献

Kindig, K.,Gibbs, E.,Seiferth, D.,Biggin, P.C.,Chakrapani, S.
Mechanisms underlying modulation of human GlyR alpha 3 by Zn 2+ and pH.
Sci Adv, 10:eadr5920-eadr5920, 2024

PubMed Abstract: Glycine receptors (GlyRs) regulate motor control and pain processing in the central nervous system through inhibitory synaptic signaling. The subtype GlyRα3 expressed in nociceptive sensory neurons of the spinal dorsal horn is a key regulator of physiological pain perception. Disruption of spinal glycinergic inhibition is associated with chronic inflammatory pain states, making GlyRα3 an attractive target for pain treatment. GlyRα3 activity is modulated by numerous endogenous and exogenous ligands that consequently affect pain sensitization. To understand the mechanism of two such endogenous modulators, Zn and protons, we have used cryo-electron microscopy to determine structures of full-length human GlyRα3 in various functional states. Whereas acidic pH reduces peak glycine response, Zn displays biphasic modulation in a concentration-dependent manner. Our findings reveal the effector sites and also capture intermediate conformations in the gating cycle. Combined with molecular dynamics simulations and electrophysiology, this work provides important insights into GlyRα3 activation and regulation.

PubMed: 39693447
DOI: 10.1126/sciadv.adr5920

実験手法

ELECTRON MICROSCOPY (2.19 Å)