ArticleChannels (Austin, Tex.)
The Kir channel immunoglobulin domain is essential for Kir1.1 (ROMK) thermodynamic stability, trafficking and gating.
Article in Channels (Austin, Tex.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Persistent renal dysfunction post-chemotherapy: a diagnostic conundrum in pediatric cancer survivorship - a case report.BMC pediatrics · 2024Article
- Characterization of hyperactive mutations in the renal potassium channel ROMK uncovers unique effects on channel biogenesis and ion conductance.Molecular biology of the cell · 2024Article
- Genome mining yields putative disease-associated ROMK variants with distinct defects.PLoS genetics · 2023Article
- The cellular pathways that maintain the quality control and transport of diverse potassium channels.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- DIMPLE: deep insertion, deletion, and missense mutation libraries for exploring protein variation in evolution, disease, and biology.Genome biology · 2023Article
- Article
- Probing ion channel functional architecture and domain recombination compatibility by massively parallel domain insertion profiling.Nature communications · 2021Article
- Targeted insertional mutagenesis libraries for deep domain insertion profiling.Nucleic acids research · 2020Article
- Disease Associated Mutations in KBiomolecules · 2019Review
- The endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (ROMK).The Journal of biological chemistry · 2018Article
- Discovery and in Vitro Optimization of 3-Sulfamoylbenzamides as ROMK Inhibitors.ACS medicinal chemistry letters · 2018Article
- Linking chanelopathies with endoplasmic reticulum associated degradation.Channels (Austin, Tex.) · 2017Article
- Endoplasmic reticulum-associated degradation of the renal potassium channel, ROMK, leads to type II Bartter syndrome.The Journal of biological chemistry · 2017Article
- Computational and functional analyses of a small-molecule binding site in ROMK.Biophysical journal · 2015Article
- Eliciting renal failure in mosquitoes with a small-molecule inhibitor of inward-rectifying potassium channels.PloS one · 2013Article
- Virtual interactomics of proteins from biochemical standpoint.Molecular biology international · 2012Article
- Development of a selective small-molecule inhibitor of Kir1.1, the renal outer medullary potassium channel.Molecular pharmacology · 2011Article
- Discovery, characterization, and structure-activity relationships of an inhibitor of inward rectifier potassium (Kir) channels with preference for Kir2.3, Kir3.x, and Kir7.1.Frontiers in pharmacology · 2011Article
- Effects of dietary K on cell-surface expression of renal ion channels and transporters.American journal of physiology. Renal physiology · 2010Article
- Conformational changes during the gating of a potassium channel revealed by structural mass spectrometry.Structure (London, England : 1993) · 2010Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The renal inward rectifying potassium channel Kir1.1 plays key roles in regulating electrolyte homeostasis and blood pressure. Loss-of-function mutations in the channel cause a life-threatening salt and water balance disorder in infants called antenatal Bartter syndrome (ABS). Of more than 30 ABS mutations identified, approximately half are located in the intracellular domain of the channel. The mechanisms underlying channel dysfunction for most of these mutations are unknown. By mapping intracellular mutations onto an atomic model of Kir1.1, we found that several of these are localized to a phylogenetically ancient immunoglobulin (Ig)-like domain (IgLD) that has not been characterized previously, prompting us to examine this structure in detail. The IgLD is assembled from two beta-pleated sheets packed face-to-face, creating a beta-sheet interface or core, populated by highly conserved side chains. Thermodynamic calculations on computationally mutated channels suggest that IgLD core residues are among the most important residues for determining cytoplasmic domain stability. Consistent with this notion, we show that two ABS mutations (A198T and Y314C) located within the IgLD core impair channel biosynthesis and trafficking in mammalian cells. A fraction of core mutant channels reach the cell surface, but are electrically silent due to closure of the helix-bundle gate. Compensatory mutation-induced rescue of channel function revealed that IgLD core mutants fail to rectify. Our study sheds new light on the pathogenesis of ABS and establishes the IgLD as an essential structure within the Kir channel family.
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