The Pentameric Ligand-Gated Ion Channel Family: A New Member of the Voltage Gated Ion Channel Superfamily?

The Pentameric Ligand-Gated Ion Channel Family: A New Member of the Voltage Gated Ion Channel Superfamily?

In this report we present seven lines of bioinformatic evidence supporting the conclusion that the Pentameric Ligand-gated Ion Channel (pLIC) Family is a member of the Voltage-gated Ion Channel (VIC) Superfamily. In our approach, we used the Transporter Classification Database (TCDB) as a reference...

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Bibliographic Details
Published in:International journal of molecular sciences Vol. 25; no. 9; p. 5005
Main Authors: Dubey, Aditi, Baxter, Madison, Hendargo, Kevin J, Medrano-Soto, Arturo, Saier, Jr, Milton H
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 01-05-2024
Subjects:
Amino Acid Sequence
Animals
bioinformatics
Computational Biology - methods
homology
Humans
Ligand-Gated Ion Channels - chemistry
Ligand-Gated Ion Channels - genetics
Ligand-Gated Ion Channels - metabolism
Ligands
Markov Chains
Markov processes
Models, Molecular
Multigene Family
Phylogeny
pLIC family
Protein Domains
Proteins
Protons
Sensors
Signal transduction
TCDB
VIC superfamily
Australia
VIC superfamily
TCDB
homology
pLIC family
bioinformatics
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Summary:In this report we present seven lines of bioinformatic evidence supporting the conclusion that the Pentameric Ligand-gated Ion Channel (pLIC) Family is a member of the Voltage-gated Ion Channel (VIC) Superfamily. In our approach, we used the Transporter Classification Database (TCDB) as a reference and applied a series of bioinformatic methods to search for similarities between the pLIC family and members of the VIC superfamily. These include: (1) sequence similarity, (2) compatibility of topology and hydropathy profiles, (3) shared domains, (4) conserved motifs, (5) similarity of Hidden Markov Model profiles between families, (6) common 3D structural folds, and (7) clustering analysis of all families. Furthermore, sequence and structural comparisons as well as the identification of a 3-TMS repeat unit in the VIC superfamily suggests that the sixth transmembrane segment evolved into a re-entrant loop. This evidence suggests that the voltage-sensor domain and the channel domain have a common origin. The classification of the pLIC family within the VIC superfamily sheds light onto the topological origins of this family and its evolution, which will facilitate experimental verification and further research into this superfamily by the scientific community.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25095005