27 results found
    1. Biochemistry and Chemical Biology

    Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes

    Nadinath B Nillegoda et al.
    The emergence of complementary electrostatic potentials after the prokaryotic-to-eukaryotic split drives physical and functional cooperation between canonical class A and class B J-proteins to boost protein disaggregation.
    1. Biochemistry and Chemical Biology

    Adenosine diphosphate restricts the protein remodeling activity of the Hsp104 chaperone to Hsp70 assisted disaggregation

    Agnieszka Kłosowska et al.
    Hsp70 chaperone provides Hsp104 with high efficiency in disaggregation and specificity towards aggregated substrates at the, otherwise limiting, cellular concentrations of adenine nucleotides.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural basis for the disaggregase activity and regulation of Hsp104

    Alexander Heuck et al.
    Protein disaggregases employ two mechanically-linked ATPase rings that are under steric control by a wrapped-around coiled-coil belt.
    1. Biochemistry and Chemical Biology
    2. Genetics and Genomics

    Therapeutic genetic variation revealed in diverse Hsp104 homologs

    Zachary M March et al.
    Exploring natural Hsp104 variation reveals unexpected tuning of a passive activity that inhibits aggregation of specific substrates to selectively counter TDP-43 or alpha-synuclein proteotoxicity connected to neurodegenerative disease.
    1. Biochemistry and Chemical Biology

    Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations

    Ryan R Cupo, James Shorter
    Skd3 (human ClpB) is a potent ATP-dependent mitochondrial protein disaggregase that is activated by the rhomboid protease, PARL, and inactivated by MGCA7-linked mutations.
    1. Structural Biology and Molecular Biophysics

    Promiscuous binding by Hsp70 results in conformational heterogeneity and fuzzy chaperone-substrate ensembles

    Rina Rosenzweig et al.
    Multiple chaperone binding sites on substrates suggest a mechanism by which the Hsp70 chaperone can circumvent kinetic traps in protein folding.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Molecular insights into substrate recognition and discrimination by the N-terminal domain of Lon AAA+ protease

    Shiou-Ru Tzeng et al.
    The N-terminal domains enable Lon protease to discriminate and capture selected protein species for degradation by exposed hydrophobic patches and flexible linkages to the hexameric core complex.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    Unified single-cell analysis of testis gene regulation and pathology in five mouse strains

    Min Jung et al.
    A statistical method for summarizing single-cell gene expression data identifies normal and disease-specific transcriptional programs from an atlas of 57,600 cells.
    1. Cell Biology
    2. Developmental Biology

    Protein aggregates are associated with replicative aging without compromising protein quality control

    Juha Saarikangas, Yves Barral
    The aging lineage of budding yeast is differentiated by an early-appearing protein deposit that promotes protein quality control.

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