Voltage-gated hydrogen channel 1 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the HVCN1
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Voltage-gated hydrogen channel 1 is a
voltage-gated proton channel
Voltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such tha ...
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 cel ...
s
and out of many types of cells including
spermatozoa
A spermatozoon (; also spelled spermatozoön; : spermatozoa; ) is a motile sperm cell (biology), cell produced by male animals relying on internal fertilization. A spermatozoon is a moving form of the ploidy, haploid cell (biology), cell that is ...
,
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 channel
Voltage-gated potassium channels (VGKCs) are potassium channel, transmembrane channels specific for potassium and Voltage-gated ion channel, sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a ...
s 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.
Classification
They are classified into 2 types:
Function
In exc ...
.
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
In 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 are small molecules; ...
inhibitors of the HVCN1 channel are being developed as
chemotherapeutic
Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) in a standard regimen. Chemotherapy may be given with a curat ...
s and
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...
agents.
References
Further reading
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{{Ion channels, g4
Ion channels