Voltage-gated hydrogen channel 1 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the HVCN1
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Voltage-gated hydrogen channel 1 is a
voltage-gated proton channel that has been shown to allow proton transport into
phagosome
In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs).
A phagosome is formed by the fusion of the cell ...
s
and out of many types of cells including
spermatozoa
A spermatozoon (; also spelled spermatozoön; ; ) is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote. (A zygote is a single cell, with a complete set of chromos ...
,
electrically excitable cells and
respiratory epithelial cells.
The proton-conducting HVCN1 channel has only transmembrane domains corresponding to the S1-S4 voltage sensing domains (VSD) of
voltage-gated potassium channels and
voltage-gated sodium channels
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the chann ...
.
Molecular simulation is consistent with a water-filled pore that can function as a "
water wire" for allowing hydrogen bonded H
+ to cross the membrane.
However, mutation of Asp112 in human Hv1 results in anion permeation, suggesting that obligatory protonation of Asp produces proton selectivity. Quantum mechanical calculations show that the Asp-Arg interaction can produce proton selective permeation.
The HVCN1 protein has been shown to exist as a dimer with two functioning pores.
Like other VSD channels, HVCN1 channels conduct ions about 1000-fold slower than channels formed by tetrameric S5-S6 central pores.
As a drug target
Small molecule
Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ...
inhibitors of the HVCN1 channel are being developed as
chemotherapeutic
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothera ...
s and
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...
agents.
References
Further reading
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{{Ion channels, g4
Ion channels