5SXV

X-ray structure of 2-bromoethanol bound to a pentameric ligand gated ion channel (ELIC) in a resting state

Summary for 5SXV

• Entry DOI: 10.2210/pdb5sxv/pdb
• Related: 5SXU
• Descriptor: Cys-loop ligand-gated ion channel, 2-BROMOETHANOL, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: elic, anesthetic, ethanol, resting state, transport protein
• Biological source: Dickeya chrysanthemi (Pectobacterium chrysanthemi)
• Total number of polymer chains: 10
• Total formula weight: 374741.25

Authors

Chen, Q.,Kinde, M.,Cohen, A.,Xu, Y.,Tang, P. (deposition date: 2016-08-10, release date: 2017-06-21, Last modification date: 2023-10-04)

Primary citation

Chen, Q.,Wells, M.M.,Tillman, T.S.,Kinde, M.N.,Cohen, A.,Xu, Y.,Tang, P.
Structural Basis of Alcohol Inhibition of the Pentameric Ligand-Gated Ion Channel ELIC.
Structure, 25:180-187, 2017

PubMed Abstract: The structural basis for alcohol modulation of neuronal pentameric ligand-gated ion channels (pLGICs) remains elusive. We determined an inhibitory mechanism of alcohol on the pLGIC Erwinia chrysanthemi (ELIC) through direct binding to the pore. X-ray structures of ELIC co-crystallized with 2-bromoethanol, in both the absence and presence of agonist, reveal 2-bromoethanol binding in the pore near T237(6') and the extracellular domain (ECD) of each subunit at three different locations. Binding to the ECD does not appear to contribute to the inhibitory action of 2-bromoethanol and ethanol as indicated by the same functional responses of wild-type ELIC and mutants. In contrast, the ELIC-α1β3GABAR chimera, replacing the ELIC transmembrane domain (TMD) with the TMD of α1β3GABAR, is potentiated by 2-bromoethanol and ethanol. The results suggest a dominant role of the TMD in modulating alcohol effects. The X-ray structures and functional measurements support a pore-blocking mechanism for inhibitory action of short-chain alcohols.

PubMed: 27916519
DOI: 10.1016/j.str.2016.11.007

Experimental method

X-RAY DIFFRACTION (3.4 Å)