208 results found
    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. 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. 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

    EDEM2 stably disulfide-bonded to TXNDC11 catalyzes the first mannose trimming step in mammalian glycoprotein ERAD

    Ginto George et al.
    EDEM2 containing mannosidase homology domain functions as an initiator of endoplasmic reticulum-associated degradation of misfolded glycoproteins by conversion of Man9GlcNAc2 to Man8GlcNAc2, only when complexed with TXNDC11 containing thioredoxin-like domains.
    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. 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. Stem Cells and Regenerative Medicine

    Insulin mutations impair beta-cell development in a patient-derived iPSC model of neonatal diabetes

    Diego Balboa et al.
    Mutations causing proinsulin misfolding trigger unfolded protein response and lead to impaired proliferation and reduced mTORC1 signalling of developing beta-cells in a patient-derived induced pluripotent stem cell disease model.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    PPP1R15A-mediated dephosphorylation of eIF2α is unaffected by Sephin1 or Guanabenz

    Ana Crespillo-Casado et al.
    The notion that the drug-like small molecule Sephin1 protects against protein misfolding by selectively disrupting a cellular phosphatase is refuted.
    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.

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