7Q3H

Pentameric ligand-gated ion channel, DeCLIC at pH 7 with 10 mM EDTA

Summary for 7Q3H

• Entry DOI: 10.2210/pdb7q3h/pdb
• Related: 7Q3G
• EMDB information: 13791 13792
• Descriptor: Neur_chan_LBD domain-containing protein (1 entity in total)
• Functional Keywords: ion channel, ligand-gated channel, pentameric channel, membrane protein
• Biological source: Desulfofustis sp. PB-SRB1
• Total number of polymer chains: 5
• Total formula weight: 358669.96

Authors

Lycksell, M.,Rovsnik, U.,Hanke, A.,Howard, R.J.,Lindahl, E. (deposition date: 2021-10-27, release date: 2022-11-16, Last modification date: 2024-07-17)

Primary citation

Lycksell, M.,Rovsnik, U.,Hanke, A.,Martel, A.,Howard, R.J.,Lindahl, E.
Biophysical characterization of calcium-binding and modulatory-domain dynamics in a pentameric ligand-gated ion channel.
Proc.Natl.Acad.Sci.USA, 119:e2210669119-e2210669119, 2022

PubMed Abstract: Pentameric ligand-gated ion channels (pLGICs) perform electrochemical signal transduction in organisms ranging from bacteria to humans. Among the prokaryotic pLGICs, there is architectural diversity involving N-terminal domains (NTDs) not found in eukaryotic relatives, exemplified by the calcium-sensitive channel (DeCLIC) from a deltaproteobacterium, which has an NTD in addition to the canonical pLGIC structure. Here, we have characterized the structure and dynamics of DeCLIC through cryoelectron microscopy (cryo-EM), small-angle neutron scattering (SANS), and molecular dynamics (MD) simulations. In the presence and absence of calcium, cryo-EM yielded structures with alternative conformations of the calcium-binding site. SANS profiles further revealed conformational diversity at room temperature beyond that observed in static structures, shown through MD to be largely attributable to rigid-body motions of the NTD relative to the protein core, with expanded and asymmetric conformations improving the fit of the SANS data. This work reveals the range of motion available to the DeCLIC NTD and calcium-binding site, expanding the conformational landscape of the pLGIC family. Further, these findings demonstrate the power of combining low-resolution scattering, high-resolution structural, and MD simulation data to elucidate interfacial interactions that are highly conserved in the pLGIC family.

PubMed: 36480474
DOI: 10.1073/pnas.2210669119

Experimental method

ELECTRON MICROSCOPY (3.2 Å)