The human ether-à-go-go-related gene (hERG) encodes a K(+) channel crucial for repolarization of the cardiac action potential. EAG-related gene (ERG) channels contain a C-terminal cyclic nucleotide-binding homology domain coupled to the pore of the channel by a C-linker. Here, we report the structure of the C-linker/cyclic nucleotide-binding homology domain of a mosquito ERG channel at 2.5-Å resolution. The structure reveals that the region expected to form the cyclic nucleotide-binding pocket is negatively charged and is occupied by a short β-strand, referred to as the intrinsic ligand, explaining the lack of direct regulation of ERG channels by cyclic nucleotides. In hERG channels, the intrinsic ligand harbors hereditary mutations associated with long-QT syndrome (LQTS), a potentially lethal cardiac arrhythmia. Mutations in the intrinsic ligand affected hERG channel gating and LQTS mutations abolished hERG currents and altered trafficking of hERG channels, which explains the LQT phenotype. The structure also reveals a dramatically different conformation of the C-linker compared with the structures of the related ether-à-go-go-like K(+) and hyperpolarization-activated cyclic nucleotide-modulated channels, suggesting that the C-linker region may be highly dynamic in the KCNH, hyperpolarization-activated cyclic nucleotide-modulated, and cyclic nucleotide-gated channels.
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http://dx.doi.org/10.1073/pnas.1306887110 | DOI Listing |
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Department of Cancer Biology, Loyola University Chicago Stritch School of Medicine, Maywood, IL, 50153, USA.
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Institute of Immunology, Christian-Albrechts University and University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany. Electronic address:
T cells expressing the γδ T-cell receptor (TCR) represent a numerically small proportion of total T cells. Unlike αβ T cells they are activated by non-peptide antigens independently of MHC-presentation. γδ T cells have been recognized as a favorable prognostic marker across different tumor entities.
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Institute of Micro/Nano Materials and Devices, Ningbo University of Technology, Ningbo 315211 PR China. Electronic address:
The development of efficient photocatalysts inspired by natural photosynthesis has drawn considerable interest for sustainable hydrogen (H) production. Among the various strategies for enhancing H evolution, constructing step-scheme (S-scheme) heterojunctions has attracted extensive interest, thanks to their limited charge recombination and enhanced charge transport in comparison to the traditional photocatalytic systems. Herein, we report the engineering of a novel S-scheme heterojunction by integrating ultrathin ZnInS (ZIS) nanosheets with MOF-derived N-doped NiO porous microrods (ZIS/N-NiO) toward superior photocatalytic behaviors.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Inorgánica, Analítica y Química Física, Buenos Aires, Argentina; CONICET-Universidad de Buenos Aires, Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE), Buenos Aires, Argentina. Electronic address:
The interest in chemical interactions between inorganic sulfur species and heme compounds has grown significantly in recent years due to their physiological relevance. The model system ferric N-acetyl microperoxidase 11 (NAcMP11Fe) enables the exploration of the mechanistic aspects of the interaction between the ferric heme group and binding sulfur ligands, without the constraints imposed by a protein matrix and the stabilizing effects of distal amino acids. In this study, we investigated the coordination of disulfane (HSSH) and its conjugate base hydrodisulfide (HSS) to NAcMP11Fe.
View Article and Find Full Text PDFAdv Exp Med Biol
January 2025
Molecular Oncology, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
RANK pathway has attracted increasing interest as a promising target in breast cancer, given the availability of denosumab, an anti-RANKL drug. RANK signaling mediates progesterone-driven regulation of mammary gland development and favors breast cancer initiation by controlling mammary cell proliferation and stem cell fate. RANK activation promotes luminal mammary epithelial cell senescence, acting as an initial barrier to tumorigenesis but ultimately facilitating tumor progression and metastasis.
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