Transmembrane domain length of viral K
            <sup>+</sup>
            channels is a signal for mitochondria targeting

Balß, Jörg; Papatheodorou, Panagiotis; Mehmel, Mario; Baumeister, Dirk; Hertel, Brigitte; Delaroque, Nicolas; Chatelain, Franck C.; Minor, Daniel L.; Etten, James L. Van; Rassow, Joachim; Moroni, Anna; Thiel, Gerhard

doi:10.1073/pnas.0805709105

Cited by 40 publications

(85 citation statements)

References 26 publications

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“…They can also complement yeast (Saccharomyces cerevisiae) cells that are defective in K + uptake (Balss et al, 2008;Chatelain et al, 2009).…”

Section: Channel and Transporter Gene Products Coded By Algal Virusesmentioning

confidence: 99%

“…By contrast, the aforementioned E. siliculosus-infecting EsV virus-encoded K + channel is targeted to the mitochondria. Chimeras formed between these two ion channels established that one could change their subcellular location by altering the length of their transmembrane domain 2 (Balss et al, 2008).…”

Section: Viral K + Channels Are Ideal For Building More Complex and Mmentioning

confidence: 99%

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Potassium Ion Channels: Could They Have Evolved from Viruses?

et al. 2013

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“…They can also complement yeast (Saccharomyces cerevisiae) cells that are defective in K + uptake (Balss et al, 2008;Chatelain et al, 2009).…”

Section: Channel and Transporter Gene Products Coded By Algal Virusesmentioning

confidence: 99%

Section: Viral K + Channels Are Ideal For Building More Complex and Mmentioning

confidence: 99%

Potassium Ion Channels: Could They Have Evolved from Viruses?

et al. 2013

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“…Yeast complementation assays were conducted as described previously. (14) Yeast strain SGY1528 lacks an endogenous K + uptake system and, therefore, does not grow on media with K + concentrations of <10 mM. Complementation assays were conducted on agar plates either under nonselective conditions (100 mM K + agar plates) or under selective conditions (1 or 0.5 mM K + ).…”

Section: Constructs and Mutagenesismentioning

confidence: 99%

“…(14) The genes were cloned into the BglII and EcoRI site in the pEGFP-N2 vector without their stop codons and in frame with the downstream green fluorescent protein (EGFP). For the yeast experiments, the genes were cloned with their stop codons into the EcoRI and XhoI site of the pYES2 vector.…”

Section: Constructs and Mutagenesismentioning

confidence: 99%

Relevance of Lysine Snorkeling in the Outer Transmembrane Domain of Small Viral Potassium Ion Channels

et al. 2012

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Transmembrane domains (TMDs) are often flanked by Lys or Arg because they keep their aliphatic parts in the bilayer and their charged groups in the polar interface. Here we examine the relevance of this so-called "snorkeling" of a cationic amino acid, which is conserved in the outer TMD of small viral K + channels. Experimentally, snorkeling activity is not mandatory for Kcv PBCV-1 because K29 can be replaced by most of the natural amino acids without any corruption of function. Two similar channels, Kcv ATCV-1 and Kcv MT325 , lack a cytosolic N-terminus, and neutralization of their equivalent cationic amino acids inhibits their function. To understand the variable importance of the cationic amino acids, we reanalyzed molecular dynamics simulations of Kcv PBCV-1 and N-terminally truncated mutants; the truncated mutants mimic Kcv ATCV-1 and Kcv MT325 . Structures were analyzed with respect to membrane positioning in relation to the orientation of K29. The results indicate that the architecture of the protein (including the selectivity filter) is only weakly dependent on TMD length and protonation of K29. The penetration depth of Lys in a given protonation state is independent of the TMD architecture, which leads to a distortion of shorter proteins. The data imply that snorkeling can be important for K + channels; however, its significance depends on the architecture of the entire TMD. The observation that the most severe N-terminal truncation causes the outer TMD to move toward the cytosolic side suggests that snorkeling becomes more relevant if TMDs are not stabilized in the membrane by other domains.

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“…These yeasts are only able to survive in medium with a high K ϩ concentration. They do not grow on a selective low K ϩ medium unless they are expressing a heterologous K ϩ uptake system (19,23). Fig.…”

Section: Resultsmentioning

confidence: 99%

Membrane Anchoring and Interaction between Transmembrane Domains are Crucial for K+ Channel Function

Gebhardt¹,

Hoffgaard

Hamacher

et al. 2011

Journal of Biological Chemistry

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The small viral channel Kcv is a Kir-like K ؉ channel of only 94 amino acids. With this simple structure, the tetramer of Kcv represents the pore module of all complex K ؉ channels. To examine the structural contribution of the transmembrane domains (TMDs) to channel function, we performed Ala scanning mutagenesis of the two domains and tested the functionality of the mutants in a yeast complementation assay. The data reveal, in combination with computational models, that the upper halves of both TMDs, which face toward the external medium, are rather rigid, whereas the inner parts are more flexible. The rigidity of the outer TMD is conferred by a number of essential aromatic amino acids that face the membrane and probably anchor this domain in the bilayer. The inner TMD is intimately connected with the rigid part of the outer TMD via ⅐⅐⅐ interactions between a pair of aromatic amino acids. This structural principle is conserved within the viral K ؉ channels and also present in Kir2.2, implying a general importance of this architecture for K ؉ channel function.K ϩ channels are transmembrane proteins, which catalyze the selective and regulated flux of potassium ions across membranes. A breakthrough in understanding of structure/function correlates in these important proteins occurred with the highresolution structures determined for several K ϩ channels (1-4). Many functional properties such as selectivity and gating of K ϩ channels are now understood on the basis of the specific architecture of these channel proteins. Still, many aspects of function and regulation cannot be explained only on the basis of the protein structure. The performance of the protein also depends on the lipid environment and on the organization of the protein in this environment. Indeed, there is increasing evidence that many different properties of K ϩ channels are depending on the interaction between the protein and the surrounding host membranes (5-7). As a consequence of this dependence, many amphiphilic drugs, which target ion channels, have dual effects, one effect being directly related to an interaction with the protein and a secondary effect being mediated by modification of the bilayer properties (8).A good model system for understanding the interplay of membrane proteins with the membrane is provided by the viral potassium channel Kcv (9, 10). This Kir-like potassium channel with two transmembrane domains is, with only 94 amino acids, very small. The protein is almost completely embedded in the membrane. Only a small, 15 amino acid-long domain at the N terminus and a short turret domain between the two transmembrane domains stick out of the membrane into aqueous solution (11). It can be assumed that in this arrangement any protein/membrane interaction strongly reflects back on function.Unbiased information on the structural significance of the two transmembrane domains (TMDs) 2 and their importance for channel function can be obtained by an alanine scan of the relevant domains. In this approach, each amino acid in a primary seq...

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Transmembrane domain length of viral K ⁺ channels is a signal for mitochondria targeting

Cited by 40 publications

References 26 publications

Potassium Ion Channels: Could They Have Evolved from Viruses?

Potassium Ion Channels: Could They Have Evolved from Viruses?

Relevance of Lysine Snorkeling in the Outer Transmembrane Domain of Small Viral Potassium Ion Channels

Membrane Anchoring and Interaction between Transmembrane Domains are Crucial for K+ Channel Function

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Transmembrane domain length of viral K + channels is a signal for mitochondria targeting

Cited by 40 publications

References 26 publications

Potassium Ion Channels: Could They Have Evolved from Viruses?

Potassium Ion Channels: Could They Have Evolved from Viruses?

Relevance of Lysine Snorkeling in the Outer Transmembrane Domain of Small Viral Potassium Ion Channels

Membrane Anchoring and Interaction between Transmembrane Domains are Crucial for K+ Channel Function

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Transmembrane domain length of viral K ⁺ channels is a signal for mitochondria targeting