Voltage-gated proton channel in a dinoflagellate

Smith, Susan; Morgan, Deri; Musset, Boris; Cherny, Vladimir V.; Place, Allen R.; Hastings, J. Woodland; DeCoursey, Thomas E.

doi:10.1073/pnas.1115405108

Cited by 113 publications

(228 citation statements)

References 60 publications

(64 reference statements)

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“…When facing pathogens, the oxidative burst with plant cells is accompanied by alkalinization of the external compartment (81). Plants have Hv1-type channels, too (316,325), but so far it is not known whether they mediate proton influx into a rather pH neutral cytoplasm. The early steps in signaling, however, are associated with an increase in cytosolic calcium and concomitant depolarization of the host cell (FIG-URE 13) (157).…”

Section: Electrical Signalingmentioning

confidence: 99%

Ion Channels in Plants

Hedrich

2012

Physiological Reviews

403

322

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Since the first recordings of single potassium channel activities in the plasma membrane of guard cells more than 25 years ago, patch-clamp studies discovered a variety of ion channels in all cell types and plant species under inspection. Their properties differed in a cell type-and cell membranedependent manner. Guard cells, for which the existence of plant potassium channels was initially documented, advanced to a versatile model system for studying plant ion channel structure, function, and physiology. Interestingly, one of the first identified potassium-channel genes encoding the Shaker-type channel KAT1 was shown to be highly expressed in guard cells. KAT1-type channels from Arabidopsis thaliana and its homologs from other species were found to encode the K ϩ -selective inward rectifiers that had already been recorded in early patch-clamp studies with guard cells. Within the genome era, additional Arabidopsis Shaker-type channels appeared. All nine members of the Arabidopsis Shaker family are localized at the plasma membrane, where they either operate as inward rectifiers, outward rectifiers, weak voltage-dependent channels, or electrically silent, but modulatory subunits. The vacuole membrane, in contrast, harbors a set of two-pore K ϩ channels. Just very recently, two plant anion channel families of the SLAC/SLAH and ALMT/QUAC type were identified. SLAC1/SLAH3 and QUAC1 are expressed in guard cells and mediate Slow-and Rapid-type anion currents, respectively, that are involved in volume and turgor regulation. Anion channels in guard cells and other plant cells are key targets within often complex signaling networks. Here, the present knowledge is reviewed for the plant ion channel biology. Special emphasis is drawn to the molecular mechanisms of channel regulation, in the context of model systems and in the light of evolution.

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Section: Electrical Signalingmentioning

confidence: 99%

Ion Channels in Plants

Hedrich

2012

Physiological Reviews

403

322

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“…EPR solvent accessibility data from hH V 1 favored the CiVSP-based model. This is reasonable, because phylogenetically, H V 1 are related more closely to VSP than to other channels (24). Although the closed hH V 1 model agrees well with the structure of the closed mH V 1 chimera, parts of S2 and S3 from the CiVSP-based model must be shifted up or down to match the crystal structure.…”

mentioning

confidence: 98%

Structural revelations of the human proton channel

DeCoursey

2015

Proc. Natl. Acad. Sci. U.S.A.

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The voltage-gated proton channel, H V 1, is notoriously unique among ion channels (1), and plays key roles in the health and disease of diverse tissues and species (2). Li et al. (3) combine biochemical, computational, and electron paramagnetic resonance (EPR) spectroscopic approaches to shed light on structural aspects of the human proton channel, hH V 1. Their results advance the field in several key areas, culminating in a bold new model for gating.The voltage-sensing domain (VSD) is the part of voltage-gated ion channels that senses the electrical potential across the cell membrane where the channel resides. Most such channels open upon membrane depolarization, which is accomplished mainly by cationic amino acids located in the fourth transmembrane helical segment (S4) moving outward when the inside of the cell is made more positive. This movement is transduced from the VSD (S1-S4) to the pore region (S5-S6), opening a conduction pathway. In addition to biologically important voltagegated K + , Na + , Ca 2+ , and H + channels, other classes of membrane proteins with VSDs exist that are not channels at all. One example is a voltage-sensing phosphatase (VSP), an enzyme whose activity is regulated by membrane potential. In a landmark study in 2014 (4), the Li-Perozo group reported crystal structures for CiVSP in both "down" and "up" conformations, the first VSD-containing molecule to have structures determined in both states. Voltage-gated ion channels are closed at negative voltages, and open upon depolarization as the S4 helix moves "up" through the membrane electrical field. Because the VSP is not a channel, "closed" and "open" become "down" and "up." The gene for hH V 1 was identified only in 2006 (5). To the astonishment of everyone, the gene product bore a striking resemblance to the VSD of other voltage-gated ion channels, so much so that the simultaneously identified mouse (mH V 1) and Ciona intestinalis (CiH V 1) gene products were dubbed VSOP or "voltage sensor-only protein" (6). H V 1 has only four membrane-spanning helices (S1-S4); these sense voltage but also contain the proton conduction pathway (7).Crystal structures are great, up to a point. They provide tremendously detailed information about molecules, but they have limitations that are sometimes overlooked. They tell us about structure, but only the structure of whatever exists in the crystal. Proteins have many conformations, and one must determine or guess which one was captured during crystallization, and hope it is a native conformation and not a broken one. Forming crystals of membrane proteins is challenging, and often the protein is modified to facilitate crystallization. Ligands or chaperone-like proteins are included, parts of the molecule are truncated, chimerae are produced: whatever it takes to get a good crystal. H V 1 has not been successfully crystallized in its entirety. First came crystal structures of the C terminus alone that lacked the entire transmembrane region (8, 9). Then in 2014, the first exciting glimpse of H V 1 ap...

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“…Usually, a coupling energy of greater than 1.5 kT (∼0.89 kcal/mol) represents a significant interaction between two residues (19 (10,11,22). However, unambiguous alignment of the VSD of Kv channels and Hv1 channels remains challenging, especially for the S4 helix (23). We adopted an alignment proposed by Musset et al (12) with the modification that the first arginine in S4, Arg255, aligns with Arg312 rather than with Arg315 in the Kv1.2-2.1 channel (Fig.…”

mentioning

confidence: 99%

Hydrophobic plug functions as a gate in voltage-gated proton channels

Chamberlin

Qiu

Rebolledo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

150

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Voltage-gated proton (Hv1) channels play important roles in the respiratory burst, in pH regulation, in spermatozoa, in apoptosis, and in cancer metastasis. Unlike other voltage-gated cation channels, the Hv1 channel lacks a centrally located pore formed by the assembly of subunits. Instead, the proton permeation pathway in the Hv1 channel is within the voltage-sensing domain of each subunit. The gating mechanism of this pathway is still unclear. Mutagenic and fluorescence studies suggest that the fourth transmembrane (TM) segment (S4) functions as a voltage sensor and that there is an outward movement of S4 during channel activation. Using thermodynamic mutant cycle analysis, we find that the conserved positively charged residues in S4 are stabilized by countercharges in the other TM segments both in the closed and open states. We constructed models of both the closed and open states of Hv1 channels that are consistent with the mutant cycle analysis. These structural models suggest that electrostatic interactions between TM segments in the closed state pull hydrophobic residues together to form a hydrophobic plug in the center of the voltage-sensing domain. Outward S4 movement during channel activation induces conformational changes that remove this hydrophobic plug and instead insert protonatable residues in the center of the channel that, together with water molecules, can form a hydrogen bond chain across the channel for proton permeation. This suggests that salt bridge networks and the hydrophobic plug function as the gate in Hv1 channels and that outward movement of S4 leads to the opening of this gate.voltage gating | mutagenesis cycle | molecular dynamics | VSOP | blocker T he best-studied function of voltage-gated proton (Hv1) channels is in the immune system, where the activity of Hv1 channels has been shown to play a key role in charge compensation for the electron extrusion by NADPH oxidase during the respiratory burst in phagocytes (1, 2). In addition, this channel is also found in many other cell types including neurons, sperm, and lung airway epithelia cells, where it has been implicated in acid extrusion, male fertility, and the pathology of asthma, respectively (3, 4). During stroke, the activity of Hv1 channels exacerbates neuronal death (5). In 2006, two independent groups identified the genes coding for the Hv1 channel in humans (hHv1) (6) and mice and Ciona intestinalis (voltage-sensing only protein; we call it "Ci-Hv1" in this paper) (7). The sequences of Hv1/(VSOP) are homologous to the sequences of the voltagesensing domain (VSD) of other voltage-gated ion channels, such as voltage-gated sodium, potassium, and calcium channels (Nav, Kv, and Cav channels), and the voltage sensor-containing phosphatase VSP (6, 7). Hydropathy analysis of the Hv1 sequence suggests the existence of four transmembrane (TM) segments (Fig. 1A), designated S1 to S4, similar to the four TM segments of the VSD of Kv channels (Fig. S1). However, Hv1 channels lack the last two TM segments of Kv channels that make up t...

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Voltage-gated proton channel in a dinoflagellate

Cited by 113 publications

References 60 publications

Ion Channels in Plants

Ion Channels in Plants

Structural revelations of the human proton channel

Hydrophobic plug functions as a gate in voltage-gated proton channels

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