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The prokaryotic H+-gated ion channel, GlvI or GLIC (Bocquet et al., 2007), solved at 2.9 Å resolution in the open pentameric state (3EHZ_E) (Bocquet et al., 2009; Corringer et al. 2010). The basis for ion selectivity has been reported (Fritsch et al., 2011). Two stage tilting of the pore lining helices results in channel opening and closing (Zhu and Hummer, 2010). The mechanical work of opening the pore is performed primarily on the M2-M3 loop. Strong interactions of this short and conserved loop with the extracellular domain are therefore crucial to couple ligand binding to channel opening. The H+-activated GLIC has an extracellular domain between TMSs M3 and M4 but lacks the intracellular domain (ICD) which is a distinct folding domain (Goyal et al., 2011). The structural basis for alcohol modulation of GLIC has been reported (Howard et al., 2011).  The structure of the M2 TMS indicates that the charge selectivity filter is in the cytoplasmic half of the channel (Parikh et al. 2011).  Below pH 5.0, GLIC desensitizes on a time scale of minutes. During activation, the extracellular hydrophobic region undergoes changes involving outward translational movement, away from the pore axis, leading to an increase in pore diameter. The lower end of M2 remains relatively immobile (Velisetty et al., 2012). During desensitization, the intervening polar residues in the middle of M2 move closer to form a solvent-occluded barrier and thereby reveal the location of a distinct desensitization gate. In comparison to the crystal structure of GLIC, the structural dynamics of the channel in a membrane environment suggest a more loosely packed conformation with water-accessible intrasubunit vestibules penetrating from the extracellular end all the way to the middle of M2 in the closed-state (Velisetty et al. 2012).  Pore opening and closing is well understood (Zhu and Hummer 2010). X-ray structures of general anaesthetics bound to GLIC reveal a common general-anaesthetic binding site, which pre-exists in the apo-structure in the upper part of the transmembrane domain of each protomer (Nury et al., 2011). Large blockers bind in the center of the membrane, but divalent transition metal ions bind to the narrow intracellular pore entry (Hilf et al., 2010).  Alcohols and anaesthetics induce structural changes and activate ligand-gated ion channels of the LIC family by binding in intersubunit cavities (Sauguet et al. 2013; Ghosh et al. 2013).  Gating at pH 4 has been visualized by x-ray crystallography (Gonzalez-Gutierrez et al. 2013)  Site-directed spin labeling and x-ray analyses have revealed gating transition motions and mechanisms that distinguish active from desensitized states (Dellisanti et al. 2013; Sauguet et al. 2013).  Gating involves major rearrangements of the interfacial loops (Velisetty et al. 2014).  A single point mutation can change the effect of an anesthetic (desfurane; chloroform) from an inhibitor to a potentiator (Brömstrup et al. 2013).  An interhelix hydrogen bond involving His234 is important for stabilization of the open state (Rienzo et al. 2014).  The outermost M4 TMS makes distinct contributions to the maturation and gating of the related GLIC and ELIC homologs, suggesting that they exhibit divergent mechanisms of channel function (Hénault et al. 2015).  The same allosteric network may underlie the actions of various anesthetics, regardless of binding site (Joseph and Mincer 2016). GLIC and ELIC (TC# 1.A.9.9.1) may represent distinct transmembrane domain archetypes (Therien and Baenziger 2017).  Arcario et al. 2017 have demonstrate an anesthetic binding site in GLIC which is accessed through a membrane-embedded tunnel. The anesthetic interacts with a previously known site, resulting in conformational changes that produce a non-conductive state of the channel (Arcario et al. 2017).  The gating mechanism has been studied (Lev et al. 2017). R-Ketamine inhibits members of the LIC family, and the structural and dynamics basis for the assymetric inhibitory modulation of ketamine has been revealed (Ion et al. 2017). Residue E35 has been identified as a key proton-sensing residue, as neutralization of its side chain carboxylate stabilizes the active state. Thus, proton activation occurs allosterically at the level of multiple loci with a key contribution of the coupling interface between the extracellular and transmembrane domains (Nemecz et al. 2017). General anesthetics can allosterically favor closed channels by binding in the pore or favor open channels via various subsites in the transmembrane domain (Fourati et al. 2018). GLIC's gating by protonation proceeds by making use of loop F, already known as an allosteric site in other pLGICs, instead of the classic orthosteric site (Hu et al. 2018). Binding of fentanyl to its binding site within GLIC results in conformational changes that inhibit conduction through the channel (Faulkner et al. 2019). This channel and others have been studied by high-speed atomic force microscopy (HS-AFM) which has made it possible to characterized the conformational dynamics of single unlabeled transmembrane channels and transporters (Heath and Scheuring 2019).

Accession Number:Q7NDN8
Protein Name:Glr4197 protein
Molecular Weight:40986.00
Species:Gloeobacter violaceus [33072]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate ions

Cross database links:

RefSeq: NP_927143.1   
Entrez Gene ID: 2602600   
Pfam: PF02931    PF02932   
BioCyc: GVIO251221:GLR4197-MONOMER   
KEGG: gvi:glr4197   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005230 F:extracellular ligand-gated ion channel acti...
GO:0006811 P:ion transport

References (1)

[1] “Complete genome structure of Gloeobacter violaceus PCC 7421, a cyanobacterium that lacks thylakoids.”  Nakamura   14621292
3EAM   3EHZ   3EI0   3IGQ   2XQ3   2XQ4   2XQ5   2XQ6   2XQ7   2XQ8   [...more]

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FASTA formatted sequence