Publication Abstract from PubMed
Voltage-gated sodium channels have essential roles in electrical signalling. Prokaryotic sodium channels are tetramers consisting of transmembrane (TM) voltage-sensing and pore domains, and a cytoplasmic carboxy-terminal domain. Previous crystal structures of bacterial sodium channels revealed the nature of their TM domains but not their C-terminal domains (CTDs). Here, using electron paramagnetic resonance (EPR) spectroscopy combined with molecular dynamics, we show that the CTD of the NavMs channel from Magnetococcus marinus includes a flexible region linking the TM domains to a four-helix coiled-coil bundle. A 2.9 A resolution crystal structure of the NavMs pore indicates the position of the CTD, which is consistent with the EPR-derived structure. Functional analyses demonstrate that the coiled-coil domain couples inactivation with channel opening, and is enabled by negatively charged residues in the linker region. A mechanism for gating is proposed based on the structure, whereby splaying of the bottom of the pore is possible without requiring unravelling of the coiled-coil.
Role of the C-terminal domain in the structure and function of tetrameric sodium channels.,Bagneris C, Decaen PG, Hall BA, Naylor CE, Clapham DE, Kay CW, Wallace BA Nat Commun. 2013 Sep 20;4:2465. doi: 10.1038/ncomms3465. PMID:24051986[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
