Research

Jump to: Review

Open AccessArticle

Modulation of Voltage-Gating and Hysteresis of Lysenin Channels by Cu²⁺ Ions

by

,

,

,

,

and

Int. J. Mol. Sci. 2023, 24(16), 12996; https://doi.org/10.3390/ijms241612996 - 20 Aug 2023

Viewed by 318

Abstract

The intricate voltage regulation presented by lysenin channels reconstituted in artificial lipid membranes leads to a strong hysteresis in conductance, bistability, and memory. Prior investigations on lysenin channels indicate that the hysteresis is modulated by multivalent cations which are also capable of eliciting [...] Read more.

The intricate voltage regulation presented by lysenin channels reconstituted in artificial lipid membranes leads to a strong hysteresis in conductance, bistability, and memory. Prior investigations on lysenin channels indicate that the hysteresis is modulated by multivalent cations which are also capable of eliciting single-step conformational changes and transitions to stable closed or sub-conducting states. However, the influence on voltage regulation of Cu²⁺ ions, capable of completely closing the lysenin channels in a two-step process, was not sufficiently addressed. In this respect, we employed electrophysiology approaches to investigate the response of lysenin channels to variable voltage stimuli in the presence of small concentrations of Cu²⁺ ions. Our experimental results showed that the hysteretic behavior, recorded in response to variable voltage ramps, is accentuated in the presence of Cu²⁺ ions. Using simultaneous AC/DC stimulation, we were able to determine that Cu²⁺ prevents the reopening of channels previously closed by depolarizing potentials and the channels remain in the closed state even in the absence of a transmembrane voltage. In addition, we showed that Cu²⁺ addition reinstates the voltage gating and hysteretic behavior of lysenin channels reconstituted in neutral lipid membranes in which lysenin channels lose their voltage-regulating properties. In the presence of Cu²⁺ ions, lysenin not only regained the voltage gating but also behaved like a long-term molecular memory controlled by electrical potentials. Full article

(This article belongs to the Special Issue Membrane Channels: Mechanistic Insights)

► Show Figures

Figure 1

Open AccessArticle

The Complex Proteolipidic Behavior of the SARS-CoV-2 Envelope Protein Channel: Weak Selectivity and Heterogeneous Oligomerization

by

,

,

,

,

,

and

Int. J. Mol. Sci. 2023, 24(15), 12454; https://doi.org/10.3390/ijms241512454 - 05 Aug 2023

Viewed by 519

Abstract

The envelope (E) protein is a small polypeptide that can form ion channels in coronaviruses. In SARS coronavirus 2 (SARS-CoV-2), the agent that caused the recent COVID-19 pandemic, and its predecessor SARS-CoV-1, E protein is found in the endoplasmic reticulum–Golgi intermediate compartment (ERGIC), [...] Read more.

The envelope (E) protein is a small polypeptide that can form ion channels in coronaviruses. In SARS coronavirus 2 (SARS-CoV-2), the agent that caused the recent COVID-19 pandemic, and its predecessor SARS-CoV-1, E protein is found in the endoplasmic reticulum–Golgi intermediate compartment (ERGIC), where virion budding takes place. Several reports claim that E protein promotes the formation of “cation-selective channels”. However, whether this term represents specificity to certain ions (e.g., potassium or calcium) or the partial or total exclusion of anions is debatable. Herein, we discuss this claim based on the available data for SARS-CoV-1 and -2 E and on new experiments performed using the untagged full-length E protein from SARS-CoV-2 in planar lipid membranes of different types, including those that closely mimic the ERGIC membrane composition. We provide evidence that the selectivity of the E-induced channels is very mild and depends strongly on lipid environment. Thus, despite past and recent claims, we found no indication that the E protein forms cation-selective channels that prevent anion transport, and even less that E protein forms bona fide specific calcium channels. In fact, the E channel maintains its multi-ionic non-specific neutral character even in concentrated solutions of Ca²⁺ ions. Also, in contrast to previous studies, we found no evidence that SARS-CoV-2 E channel activation requires a particular voltage, high calcium concentrations or low pH, in agreement with available data from SARS-CoV-1 E. In addition, sedimentation velocity experiments suggest that the E channel population is mostly pentameric, but very dynamic and probably heterogeneous, consistent with the broad distribution of conductance values typically found in electrophysiological experiments. The latter has been explained by the presence of proteolipidic channel structures. Full article

(This article belongs to the Special Issue Membrane Channels: Mechanistic Insights)

► Show Figures

Figure 1

Open AccessArticle

Triplin: Mechanistic Basis for Voltage Gating

by

Marco Colombini

,

Patrick Liu

and

Chase Dee

Int. J. Mol. Sci. 2023, 24(14), 11473; https://doi.org/10.3390/ijms241411473 - 14 Jul 2023

Viewed by 341

Abstract

The outer membrane of Gram-negative bacteria contains a variety of pore-forming structures collectively referred to as porins. Some of these are voltage dependent, but weakly so, closing at high voltages. Triplin, a novel bacterial pore-former, is a three-pore structure, highly voltage dependent, with [...] Read more.

The outer membrane of Gram-negative bacteria contains a variety of pore-forming structures collectively referred to as porins. Some of these are voltage dependent, but weakly so, closing at high voltages. Triplin, a novel bacterial pore-former, is a three-pore structure, highly voltage dependent, with a complex gating process. The three pores close sequentially: pore 1 at positive potentials, 2 at negative and 3 at positive. A positive domain containing 14 positive charges (the voltage sensor) translocates through the membrane during the closing process, and the translocation is proposed to take place by the domain entering the pore and thus blocking it, resulting in the closed conformation. This mechanism of pore closure is supported by kinetic measurements that show that in the closing process the voltage sensor travels through most of the transmembrane voltage before reaching the energy barrier. Voltage-dependent blockage of the pores by polyarginine, but not by a 500-fold higher concentrations of polylysine, is consistent with the model of pore closure, with the sensor consisting mainly of arginine residues, and with the presence, in each pore, of a complementary surface that serves as a binding site for the sensor. Full article

(This article belongs to the Special Issue Membrane Channels: Mechanistic Insights)

► Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview

Mechanisms of PIEZO Channel Inactivation

by

Zijing Zhou

and

Boris Martinac

Int. J. Mol. Sci. 2023, 24(18), 14113; https://doi.org/10.3390/ijms241814113 - 14 Sep 2023

Viewed by 426

Abstract

PIEZO channels PIEZO1 and PIEZO2 are the newly identified mechanosensitive, non-selective cation channels permeable to Ca²⁺. In higher vertebrates, PIEZO1 is expressed ubiquitously in most tissues and cells while PIEZO2 is expressed more specifically in the peripheral sensory neurons. PIEZO channels [...] Read more.

PIEZO channels PIEZO1 and PIEZO2 are the newly identified mechanosensitive, non-selective cation channels permeable to Ca²⁺. In higher vertebrates, PIEZO1 is expressed ubiquitously in most tissues and cells while PIEZO2 is expressed more specifically in the peripheral sensory neurons. PIEZO channels contribute to a wide range of biological behaviors and developmental processes, therefore driving significant attention in the effort to understand their molecular properties. One prominent property of PIEZO channels is their rapid inactivation, which manifests itself as a decrease in channel open probability in the presence of a sustained mechanical stimulus. The lack of the PIEZO channel inactivation is linked to various mechanopathologies emphasizing the significance of studying this PIEZO channel property and the factors affecting it. In the present review, we discuss the mechanisms underlying the PIEZO channel inactivation, its modulation by the interaction of the channels with lipids and/or proteins, and how the changes in PIEZO inactivation by the channel mutations can cause a variety of diseases in animals and humans. Full article

(This article belongs to the Special Issue Membrane Channels: Mechanistic Insights)

► Show Figures

Figure 1

Open AccessReview

Gating of β-Barrel Protein Pores, Porins, and Channels: An Old Problem with New Facets

by

Lauren A. Mayse

and

Liviu Movileanu

Int. J. Mol. Sci. 2023, 24(15), 12095; https://doi.org/10.3390/ijms241512095 - 28 Jul 2023

Viewed by 516

Abstract

β barrels are ubiquitous proteins in the outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria. These transmembrane proteins (TMPs) execute a wide variety of tasks. For example, they can serve as transporters, receptors, membrane-bound enzymes, as well as adhesion, structural, and signaling elements. [...] Read more.

β barrels are ubiquitous proteins in the outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria. These transmembrane proteins (TMPs) execute a wide variety of tasks. For example, they can serve as transporters, receptors, membrane-bound enzymes, as well as adhesion, structural, and signaling elements. In addition, multimeric β barrels are common structural scaffolds among many pore-forming toxins. Significant progress has been made in understanding the functional, structural, biochemical, and biophysical features of these robust and versatile proteins. One frequently encountered fundamental trait of all β barrels is their voltage-dependent gating. This process consists of reversible or permanent conformational transitions between a large-conductance, highly permeable open state and a low-conductance, solute-restrictive closed state. Several intrinsic molecular mechanisms and environmental factors modulate this universal property of β barrels. This review article outlines the typical signatures of voltage-dependent gating. Moreover, we discuss recent developments leading to a better qualitative understanding of the closure dynamics of these TMPs. Full article

(This article belongs to the Special Issue Membrane Channels: Mechanistic Insights)

► Show Figures

Figure 1

Arabic	Hebrew	Polish
Bulgarian	Hindi	Portuguese
Catalan	Hmong Daw	Romanian
Chinese Simplified	Hungarian	Russian
Chinese Traditional	Indonesian	Slovak
Czech	Italian	Slovenian
Danish	Japanese	Spanish
Dutch	Klingon	Swedish
English	Korean	Thai
Estonian	Latvian	Turkish
Finnish	Lithuanian	Ukrainian
French	Malay	Urdu
German	Maltese	Vietnamese
Greek	Norwegian	Welsh
Haitian Creole	Persian

Arabic	Hebrew	Polish
Bulgarian	Hindi	Portuguese
Catalan	Hmong Daw	Romanian
Chinese Simplified	Hungarian	Russian
Chinese Traditional	Indonesian	Slovak
Czech	Italian	Slovenian
Danish	Japanese	Spanish
Dutch	Klingon	Swedish
English	Korean	Thai
Estonian	Latvian	Turkish
Finnish	Lithuanian	Ukrainian
French	Malay	Urdu
German	Maltese	Vietnamese
Greek	Norwegian	Welsh
Haitian Creole	Persian

Journal Menu

Journal Browser

Special Issue "Membrane Channels: Mechanistic Insights"

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (5 papers)

Research

Review

Planned Papers

Further Information

Guidelines

MDPI Initiatives

Follow MDPI