185 results found
    1. Computational and Systems Biology

    Unravelling druggable signalling networks that control F508del-CFTR proteostasis

    Ramanath Narayana Hegde et al.
    Analysis of the mechanism of action of cystic fibrosis corrector drugs reveals signalling pathways potently controlling the proteostasis of the main disease-relevant CFTR mutant.
    1. Biochemistry and Chemical Biology

    Gq activity- and β-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility

    Dao-Lai Zhang et al.
    ADGRG2, an orphan GPCR, when coupled to CFTR via a regional Gq signaling on the apical membrane, acts to regulate efferent duct fluid reabsorption making it essential for male fertility.
    1. Cell Biology

    Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid

    Yajamana Ramu et al.
    Tannic acid acts as an ‘antidote’ against the negative effects of a bacterial enzyme, which can both aggravate cystic fibrosis and enable the anthrax bacteria to evade the immune responses elicited by a typical live vaccine.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Obligate coupling of CFTR pore opening to tight nucleotide-binding domain dimerization

    Csaba Mihályi et al.
    Coupling of CFTR pore opening to nucleotide binding domain dimerization does not depend on ATP binding, but is an inherent property of the channel protein and likely other ABC transporters.
    1. Structural Biology and Molecular Biophysics

    Cystic fibrosis drug ivacaftor stimulates CFTR channels at picomolar concentrations

    László Csanády, Beáta Töröcsik
    Aqueous solubility of cystic fibrosis drug ivacaftor is ~200-fold lower, whereas the potency of its stimulatory effect on the CFTR channel is >100-fold higher, than reported, and is fully reversible.
    1. Immunology and Inflammation

    Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis

    Heledd H Jarosz-Griffiths et al.
    CFTR modulators have potent innate anti-inflammatory properties that can be measured in clinic, both ex vivo and in vitro, which can be used to predict treatment efficacy.
    1. Computational and Systems Biology
    2. Chromosomes and Gene Expression

    An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability

    Judith Schütte et al.
    A computer model built on insights gained from comprehensive experimental analysis reveals mechanisms of blood stem cell regulation.
    1. Structural Biology and Molecular Biophysics

    Asymmetry of movements in CFTR's two ATP sites during pore opening serves their distinct functions

    Ben Sorum et al.
    In the CFTR chloride channel, ATP bound in the catalytic site promotes pore opening, whereas ATP bound in the non-catalytic site supports unidirectional conformational cycling by preventing pore closure without ATP hydrolysis in the catalytic site.
    1. Genetics and Genomics
    2. Structural Biology and Molecular Biophysics

    SLC6A14, an amino acid transporter, modifies the primary CF defect in fluid secretion

    Saumel Ahmadi et al.
    Loss of an amino acid transporter and tissue depletion of nitric oxide worsens the intestinal function of CF mice, a finding that potentially explains variation in disease severity amongst CF individuals.
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structures and functional characterization of murine Slc26a9 reveal mechanism of uncoupled chloride transport

    Justin D Walter et al.
    The cryo-EM structure and functional characterization of the chloride-selective ion transporter Slc26a9 defines its oligomeric architecture and transport mechanism.

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