9EVB

Non-uniform refinement of the CryoEM structure of DeCLIC nanodisc with 10mM EDTA in sym-like state

Summary for 9EVB

• Entry DOI: 10.2210/pdb9evb/pdb
• EMDB information: 19997
• Descriptor: Neur_chan_LBD domain-containing protein, N-OCTANE, DECANE, ... (5 entities in total)
• Functional Keywords: ion channel, translocase
• Biological source: Desulfofustis sp. PB-SRB1
• Total number of polymer chains: 5
• Total formula weight: 363509.56

Authors

Fan, C.,Howard, R.J.,Lindahl, E. (deposition date: 2024-03-28, release date: 2025-04-09, Last modification date: 2025-12-17)

Primary citation

Fan, C.,Lycksell, M.,Zhuang, Y.,Howard, R.J.,Lindahl, E.
Calcium stabilizes the flexible N-terminal domain of the bacterial ion channel DeCLIC.
J Struct Biol X, 12:100139-100139, 2025

PubMed Abstract: Pentameric ligand-gated ion channels (pLGICs) are responsible for the rapid conversion of chemical to electrical signals. In addition to the canonical extracellular and transmembrane domains, some prokaryotic pLGICs contain an N-terminal domain (NTD) of unclear structure and function. In one such case, the calcium-sensitive channel DeCLIC, the NTD appears to accelerate gating; however, its evident flexibility has posed a challenge to model building, and its role in calcium sensitivity is unclear. Here we report cryo-EM structures of DeCLIC in circularized lipid nanodiscs, achieving the highest resolution reported so far, and enabling definition of calcium-binding sites in both the N-terminal and canonical extracellular domains. In addition to the symmetric state, calcium depletion promoted an asymmetric conformation of the NTD, offering a structural rationale for small-angle scattering results. Behavior of these structures in molecular dynamics simulations demonstrated calcium stabilization of the NTD. These features of DeCLIC offer a model system for ion-channel modulation by a flexible accessory domain, potentially conserved in structurally homologous systems across evolution.

PubMed: 41328424
DOI: 10.1016/j.yjsbx.2025.100139

Experimental method

ELECTRON MICROSCOPY (2.38 Å)