4TWF

X-ray structure of a pentameric ligand gated ion channel from Erwinia chrysanthemi (ELIC) in complex with bromomemantine

Summary for 4TWF

• Entry DOI: 10.2210/pdb4twf/pdb
• Descriptor: Cys-loop ligand-gated ion channel, Bromomemantine (2 entities in total)
• Functional Keywords: elic, lgic, cys-loop, channel, memantine, pore blocker, transport protein
• Biological source: Dickeya chrysanthemi (Pectobacterium chrysanthemi)
• Cellular location: Cell inner membrane ; Multi- pass membrane protein : P0C7B7
• Total number of polymer chains: 10
• Total formula weight: 355910.29

Authors

Ulens, C.,Spurny, R.,Thompson, A.J.,Alqazzaz, M.,Debaveye, S.,Lu, H.,Price, K.,Villalgordo, J.M.,Tresadern, G.,Lynch, J.W.,Lummis, S.C.R. (deposition date: 2014-06-30, release date: 2014-09-24, Last modification date: 2023-12-20)

Primary citation

Ulens, C.,Spurny, R.,Thompson, A.J.,Alqazzaz, M.,Debaveye, S.,Han, L.,Price, K.,Villalgordo, J.M.,Tresadern, G.,Lynch, J.W.,Lummis, S.C.
The Prokaryote Ligand-Gated Ion Channel ELIC Captured in a Pore Blocker-Bound Conformation by the Alzheimer's Disease Drug Memantine.
Structure, 22:1399-1407, 2014

PubMed Abstract: Pentameric ligand-gated ion channels (pLGIC) catalyze the selective transfer of ions across the cell membrane in response to a specific neurotransmitter. A variety of chemically diverse molecules, including the Alzheimer's drug memantine, block ion conduction at vertebrate pLGICs by plugging the channel pore. We show that memantine has similar potency in ELIC, a prokaryotic pLGIC, when it contains an F16'S pore mutation. X-ray crystal structures, using both memantine and its derivative, Br-memantine, reveal that the ligand is localized at the extracellular entryway of the channel pore, and the pore is in a more closed conformation than wild-type ELIC in both the presence and absence of memantine. However, using voltage clamp fluorometry we observe fluorescence changes in opposite directions during channel activation and pore block, revealing an additional conformational transition not apparent from the crystal structures. These results have important implications for drugs such as memantine, which block channel pores.

PubMed: 25199693
DOI: 10.1016/j.str.2014.07.013

Experimental method

X-RAY DIFFRACTION (3.901 Å)