scholarly journals Structural and functional characterization of an otopetrin family proton channel

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Qingfeng Chen ◽  
Weizhong Zeng ◽  
Ji She ◽  
Xiao-chen Bai ◽  
Youxing Jiang
Keyword(s):  
Intracellular Ph ◽  
Proton Transport ◽  
Functional Characterization ◽  
Proton Channel ◽  
Transmembrane Helices ◽  
Conserved Residues ◽  
Proton Channels ◽  
Ph Dependent ◽  
Key Residues

The otopetrin (OTOP) proteins were recently characterized as proton channels. Here we present the cryo-EM structure of OTOP3 from Xenopus tropicalis (XtOTOP3) along with functional characterization of the channel. XtOTOP3 forms a homodimer with each subunit containing 12 transmembrane helices that can be divided into two structurally homologous halves; each half assembles as an α-helical barrel that could potentially serve as a proton conduction pore. Both pores open from the extracellular half before becoming occluded at a central constriction point consisting of three highly conserved residues – Gln232/585-Asp262/Asn623-Tyr322/666 (the constriction triads). Mutagenesis shows that the constriction triad from the second pore is less amenable to perturbation than that of the first pore, suggesting an unequal contribution between the two pores to proton transport. We also identified several key residues at the interface between the two pores that are functionally important, particularly Asp509, which confers intracellular pH-dependent desensitization to OTOP channels.

scholarly journals Characterization of βαβββ Resistance Proteins from Pseudomonas aeruginosa

2014 ◽  
Vol 70 (a1) ◽  
pp. C717-C717
Author(s):  
Allegra Vit ◽  
Monika Popp ◽  
Eyad Kalawy-Fansa ◽  
Shen Yu ◽  
Wulf Blankenfeldt
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Physiological Function ◽  
Functional Characterization ◽  
Conserved Residues ◽  
X Ray ◽  
Resistance Proteins ◽  
X Ray Crystallography ◽  
Phenazine Derivative ◽  
Function Assignment

Pseudomonas aeruginosa is a multiresistant pathogen that can cause infection in immuno-compromized patients, for example in people suffering from cystic fibrosis. [1] It has complex patho-physiology and produces a large number of exoproducts, among which the phenazines are especially prominent. In P. aeruginosa, the blue phenazine derivative pyocyanin plays a crucial role in infection of the host. [2] This phenazine can generate reactive oxygen species and is thought to act as respiratory pigment and as a virulence factor at the same time. P. aeruginosa has to protect itself from its own phenazines because of the antibiotic action of these substances. Inspired by the fact that the phenazine biosynthesis operon of several bacteria contains a phenazine resistance factor of the βαβββ module protein family, we have searched the genome of P. aeruginosa for proteins of this fold. [3] In P. aeruginosa we could identify 22 of these genes, most without previous functional characterization. A structure-based sequence alignment made it possible to assign these proteins to two classes with two subgroups each, based on the conserved residues in the active site. Using X-ray crystallography and biophysical methods, we further demonstrate that several of these proteins indeed bind phenazines and possibly other antibiotics that contain aromatic moieties. Currently, we are working on the structural characterization and physiological function assignment of all of these βαβββ-module-containing proteins. Ultimately, these data may lead to novel anti-infective strategies.

scholarly journals Discovery and characterization of Hv1-type proton channels in reef-building corals.

2021 ◽  
Author(s):  
Gisela Rangel-Tescas ◽  
Cecilia Cervantes ◽  
Miguel A Cervantes-Rocha ◽  
Esteban Suarez-Delgado ◽  
Anastazia T Banaszak ◽  
...  
Keyword(s):  
Voltage Dependence ◽  
Ph Regulation ◽  
Functional Characterization ◽  
Gene Encoding ◽  
Proton Channels ◽  
Gating Model ◽  
Mechanistic Insight ◽  
Voltage Dependent ◽  
Insight Into

Voltage-dependent proton-permeable channels are membrane proteins mediating a number of important physiological functions. Here we report the presence of a gene encoding for Hv1 voltage-dependent, proton-permeable channels in two species of reef-building corals. We performed a characterization of their biophysical properties and found that these channels are fast-activating and modulated by the pH gradient in a manner that makes them interesting models for studying these processes more easily. We have also developed an allosteric gating model that provides mechanistic insight into the modulation of voltage-dependence by protons. This work also represents the first functional characterization of any ion channel in scleractinian corals. We discuss the implications of the presence of these channels in the membranes of coral cells in the calcification and pH regulation processes and possible consequences of ocean acidification related to the function of these channels.

Can viral envelope proteins act as or induce proton channels?

1987 ◽  
Vol 7 (10) ◽  
pp. 761-769 ◽  
Author(s):  
C. Kempf ◽  
M. R. Michel ◽  
U. Kohler ◽  
H. Koblet
Keyword(s):  
Plasma Membrane ◽  
Intracellular Ph ◽  
Viral Envelope ◽  
Proton Channel ◽  
Acidic Ph ◽  
Enveloped Viruses ◽  
Sudden Drop ◽  
Proton Channels ◽  
Common Features ◽  
Vesicular Stomatitis

The mechanism of the process leading to cell-cell fusion induced by enveloped viruses at a mildly acidic pH is as yet unknown. In this report we demonstrate that the fusion events induced by three viruses of different families, namely Semliki Forest (togavirus), vesicular stomatitis (rhabdovirus) and influenza (orthomyxovirus), share common features. In all three systems a sudden drop of the intracellular pH—below the critical eextracellular pH required to trigger “fusion from within” (FFWI)—is observed. This influx of protons is specific and not due to a general leakiness of the plasma membrane, and therefore might be caused by the opening of a proton channel.

scholarly journals Author response: Structural and functional characterization of an otopetrin family proton channel

2019 ◽  
Author(s):  
Qingfeng Chen ◽  
Weizhong Zeng ◽  
Ji She ◽  
Xiao-chen Bai ◽  
Youxing Jiang
Keyword(s):  
Functional Characterization ◽  
Proton Channel ◽  
Author Response

scholarly journals Molecular and Functional Characterization of Hv1 Proton Channel in Human Granulocytes

PLoS ONE ◽  
2010 ◽  
Vol 5 (11) ◽  
pp. e14081 ◽  
Author(s):  
Gábor L. Petheő ◽  
Anna Orient ◽  
Mónika Baráth ◽  
István Kovács ◽  
Bence Réthi ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Proton Channel ◽  
Human Granulocytes

scholarly journals Structures of the Otopetrin Proton Channels Otop1 and Otop3

2019 ◽  
Author(s):  
Kei Saotome ◽  
Bochuan Teng ◽  
Che Chun (Alex) Tsui ◽  
Wen-Hsin Lee ◽  
Yu-Hsiang Tu ◽  
...  
Keyword(s):  
Taste Receptor ◽  
Salt Bridge ◽  
Proton Channel ◽  
Structural Basis ◽  
Transmembrane Helices ◽  
Proton Channels ◽  
Selective Channel ◽  
Functional Relevance ◽  
Dynamics Simulations ◽  
Lipid Nanodiscs

Otopetrins (Otop1-Otop3) comprise one of only two known eukaryotic proton-selective channel families. Otop1 is required for formation of otoconia and is a candidate mammalian sour taste receptor. Here, we report cryo-EM structures of zebrafish Otop1 and chicken Otop3 in lipid nanodiscs. The structures reveal a dimeric architecture of Otopetrins with each subunit consisting of twelve transmembrane helices divided into structurally related N and C domains. Cholesterol-like molecules occupy various sites in Otop1 and Otop3 and occlude a cavernous central tunnel. Two hydrophilic vestibules, as well as the intrasubunit interface between N and C domains, form conduits for water entry into the membrane plane in molecular dynamics simulations, suggesting they each could provide pathways for proton conduction. We also demonstrate the functional relevance of a salt bridge in the C domain vestibule by mutagenesis. Our results provide a structural basis for understanding the function of the Otopetrin proton channel family.

scholarly journals Molecular and functional characterization of the voltage-gated proton channel in zebrafish neutrophils

2017 ◽  
Vol 5 (15) ◽  
pp. e13345 ◽  
Author(s):  
Adisorn Ratanayotha ◽  
Takafumi Kawai ◽  
Shin-ichi Higashijima ◽  
Yasushi Okamura
Keyword(s):  
Functional Characterization ◽  
Proton Channel ◽  
Voltage Gated
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