245 results found
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Monitoring site-specific conformational changes in real-time reveals a misfolding mechanism of the prion protein

    Ishita Sengupta, Jayant Udgaonkar
    Multi-site FRET measurements of moPrP oligomerization at low pH indicate that major conformational changes take place as monomers reversibly transform into large oligomers, which subsequently disassemble reversibly into small oligomers.
    1. Cell Biology

    Spatial quality control bypasses cell-based limitations on proteostasis to promote prion curing

    Courtney L Klaips et al.
    Cell division imposes a limit on proteostasis capacity by reducing chaperone accumulation, but chaperone-substrate interactions reverse these events to allow clearance of even chronically misfolded protein amyloids.
    1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    Small molecule-mediated refolding and activation of myosin motor function

    Michael B Radke et al.
    The small molecule EMD 57033 is one of a new class of pharmacological chaperones that stabilize, enhance the activity of, and correct stress-induced misfolding of myosin proteins.
    1. Cell Biology

    Cytoplasmic protein misfolding titrates Hsp70 to activate nuclear Hsf1

    Anna E Masser et al.
    Hsp70 restricts DNA binding activity of Hsf1 to control the width and amplitude of the heat-shock regulon.
    1. Structural Biology and Molecular Biophysics

    Microsecond sub-domain motions and the folding and misfolding of the mouse prion protein

    Rama Reddy Goluguri et al.
    Native state dynamics of mouse prion protein were measured, and these motions were shown to be having a role in initiation of aggregation.
    1. Cell Biology

    Nuclear export of misfolded SOD1 mediated by a normally buried NES-like sequence reduces proteotoxicity in the nucleus

    Yongwang Zhong et al.
    Cellular and genetic approaches reveal that exposure of a normally buried nuclear export signal (NES)-like sequence mediates export of ALS-linked mutant and misfolded wild-type SOD1 to the cytoplasm by CRM1.
    1. Cancer Biology
    2. Computational and Systems Biology

    Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome

    Amanda B Abildgaard et al.
    Biophysical modeling, performed in silico, can predict the abundance, metabolic stability, and function of MLH1 inside living cells.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    Hsp70-associated chaperones have a critical role in buffering protein production costs

    Zoltán Farkas et al.
    Protein biosynthesis and protein quality control jointly determine protein production costs.
    1. Cell Biology

    CHIP as a membrane-shuttling proteostasis sensor

    Yannick Kopp et al.
    The mechanism is revealed that connects the protein degradation machinery to cellular membrane-bound compartments during proteostasis stress in mammalian cells.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Mitochondria supply ATP to the ER through a mechanism antagonized by cytosolic Ca2+

    Jing Yong et al.
    ATP enters the endoplasmic reticulum (ER) lumen through an SLC35B1/AXER-dependentCaATiER mechanism, and ATP usage in the ER renders 'anti-Warburg' effect by increasing ATP regeneration from OxPhos while decreasing glycolysis.

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