Advertisement

Topics

The calmodulin-binding tetraleucine motif of KCNE4 is responsible for association with Kv1.3.

08:00 EDT 10th April 2019 | BioPortfolio

Summary of "The calmodulin-binding tetraleucine motif of KCNE4 is responsible for association with Kv1.3."

The voltage-dependent potassium (Kv) channel Kv1.3 regulates leukocyte proliferation, activation, and apoptosis, and altered expression of this channel is linked to autoimmune diseases. Thus, the fine-tuning of Kv1.3 function is crucial for the immune system response. The Kv1.3 accessory protein, potassium voltage-gated channel subfamily E (KCNE) subunit 4, acts as a dominant negative regulatory subunit to both enhance inactivation and induce intracellular retention of Kv1.3. Mutations in KCNE4 also cause immune system dysfunction. Although the formation of Kv1.3-KCNE4 complexes has profound consequences for leukocyte physiology, the molecular determinants involved in the Kv1.3-KCNE4 association are unknown. We now show that KCNE4 associates with Kv1.3 via a tetraleucine motif situated within the carboxy-terminal domain of this accessory protein. This motif would function as an interaction platform, in which Kv1.3 and Ca/calmodulin compete for the KCNE4 interaction. Finally, we propose a structural model of the Kv1.3-KCNE4 complex. Our experimental data and the in silico structure suggest that the KCNE4 interaction hides a forward-trafficking motif within Kv1.3 in addition to adding a strong endoplasmic reticulum retention signature to the Kv1.3-KCNE4 complex. Thus, the oligomeric composition of the Kv1.3 channelosome fine-tunes the precise balance between anterograde and intracellular retention elements that control the cell surface expression of Kv1.3 and immune system physiology.-Solé, L., Roig, S. R., Sastre, D., Vallejo-Gracia, A., Serrano-Albarrás, A., Ferrer-Montiel, A., Fernández-Ballester, G., Tamkun, M. M., Felipe, A. The calmodulin-binding tetraleucine motif of KCNE4 is responsible for association with Kv1.3.

Affiliation

Journal Details

This article was published in the following journal.

Name: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Pages: fj201801164RR

Links

DeepDyve research library

PubMed Articles [17947 Associated PubMed Articles listed on BioPortfolio]

Crystal structures of the N-terminal domain of the Staphylococcus aureus DEAD-box RNA helicase CshA and its complex with AMP.

CshA is a DEAD-box RNA helicase that belongs to the DExD/H-box family of proteins, which generally have an RNA-dependent ATPase activity. In Staphylococcus aureus, CshA was identified as a component o...

Role of tau N-terminal motif in the secretion of human tau by End Binding proteins.

For unknown reasons, humans appear to be particular susceptible to developing tau pathology leading to neurodegeneration. Transgenic mice are still undoubtedly the most popular and extensively used an...

Kcne4 deletion sex-dependently inhibits the RISK pathway response and exacerbates hepatic ischemia-reperfusion injury in mice.

Activation of anti-apoptotic signaling cascades such as the reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways is protective in a variety of tissues in...

DNA Motif Recognition Modeling from Protein Sequences.

Although the existing works on DNA motif discovery on DNA sequences are plethoric, mechanistic knowledge to infer DNA motifs from protein sequences across multiple DNA-binding domain families without ...

Increased fes1a thermotolerance is induced by BAG6 knockout.

KEY MESSAGE: (1) The fes1a bag6 double mutant shows an increased short term thermotolerance compared to fes1a. BAG6 is a suppressor of Fes1A; (2) IQ motif is essential to effective performance of BAG6...

Clinical Trials [3027 Associated Clinical Trials listed on BioPortfolio]

Genetic Determinants of the Bronchodilatation Effect of Albuterol ex-Vivo

The role played by ß2AR polymorphisms in determining the bronchial response to ß2AR agonist drugs, has been confirmed by several studies. The purpose of the present study is to examine ...

Sodium Channel Splicing in Obstructive Sleep Apnea (SOCS-OSA)

This study is designed to test whether SCN5A mRNA processing is altered in OSA patients, which may contribute to their increased arrhythmic risk, and whether processing of SCN5A mRNA is mo...

First-in-Human Positron Emission Tomography Study Using the 18F-αvβ6-Binding-Peptide

This clinical trial studies the side effects of 18F-alphavbeta6-binding-peptide and how well it works in imaging patients with primary or cancer that has spread to the breast, colorectal, ...

Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter and Its Relevance for Rapid Antidepressant Response

Intravenous application of ketamine is currently dramatically gaining in significance as a rapid and highly effective antidepressant treatment option. Ketamine modulates various neurotrans...

Study of the Role of Soluble Inhibitor of Interleukin 22, Interleukin 22 Binding Protein (IL-22BP), in Chronic Inflammatory Bowel Disease

IL-22 is an IL-10 family cytokine that plays major actions to increase intestinal epithelial barrier function and regeneration during experimental colitis. IL-22 binding protein is a small...

Medical and Biotech [MESH] Definitions

A family of RNA-BINDING PROTEINS that contain an RNA RECOGNITION MOTIF and two ribonucleoprotein (RNP) domains which bind RNA, in addition to other domains that allow for high affinity binding, sequence specificity, and protein interactions. Examples of RNA recognition motif proteins include HETEROGENEOUS NUCLEAR RIBONUCLEARPROTEINS (hnRNP) and EMBRYONIC LETHAL ABNORMAL-VISION (ELAV) proteins.

Proteins which bind calmodulin. They are found in many tissues and have a variety of functions including F-actin cross-linking properties, inhibition of cyclic nucleotide phosphodiesterase and calcium and magnesium ATPases.

A helix-turn-helix motif characterized by three alpha-helices and four-stranded beta-sheets arranged in the order alpha1-beta1-beta2-alpha2-alpha3-beta3-beta4. The third alpha-helix contacts the major groove of DNA. The ETS motif and the flanking amino acid sequences of Ets proteins influence the binding affinity, and the alteration of a single amino acid in the Ets domain can change its DNA binding specificity.

An RNA-binding motif characterized by an alpha-beta-beta-beta-alpha fold that binds DOUBLE-STRANDED RNA. It occurs in many eukaryotic proteins as well as in bacterial and viral proteins.

An approximately 80 amino acid RNA binding motif that consists of four anti-parallel surface beta sheets and two alpha helices arranged in a beta-alpha-beta-beta-alpha-beta configuration. One of the surface beta sheets interacts with two or three specific RNA bases. Interactions between additional sequences and the RNA, as well as within the RNA recognition motif increase the affinity and specificity of the protein-RNA interaction.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Autoimmune Disorders
Autoimmune disorders are conditions that occurs when the immune system mistakenly attacks and destroys healthy body tissue. There are more than 80 different types of autoimmune disorders. Normally the immune system's white blood cells help protect ...

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...


Searches Linking to this Article