Chaperones articles within Nature Communications

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  • Article
    | Open Access

    A pool of quality control proteins (QC) maintains the protein-folding homeostasis in the cell, but its quantitative analysis is challenging. Here the authors develop a FRET sensor based on the protein barnase, able to quantify QC holdase activity and its ability to suppress protein aggregation.

    • Rebecca J. Wood
    • , Angelique R. Ormsby
    •  & Danny M. Hatters

  • Article
    | Open Access

    The Hsp90 chaperone cycle is influenced by multiple phosphorylation events but their regulatory functions are poorly understood. Here, the authors show that phosphorylation and unfolding of cochaperone Cdc37 tailors the Hsp90 chaperone cycle by recruiting kinases that promote distinct phosphorylation patterns.

    • Ashleigh B. Bachman
    • , Dimitra Keramisanou
    •  & Ioannis Gelis

  • Article
    | Open Access

    Protein phosphatase 2A (PP2A) forms different holoenzymes but little is known about the disassembly of these important signalling complexes. Here the authors present the crystal structure of PP2A bound to TOR signaling pathway regulator (TIPRL) and give insights into the methylation-dependent disassembly of PP2A holenzymes.

    • Cheng-Guo Wu
    • , Aiping Zheng
    •  & Yongna Xing

  • Article
    | Open Access

    The BRICHOS domain is a chaperone that can act against amyloid-β peptide fibril formation and non-fibrillar protein aggregation. Here the authors use a multidisciplinary approach and show that the Bri2 BRICHOS domain has qualitatively different chaperone activities depending on its quaternary structure.

    • Gefei Chen
    • , Axel Abelein
    •  & Jan Johansson

  • Article
    | Open Access

    The bacterial chaperone Trigger Factor (TF) is a dynamic protein and its dimer structure is unknown. Here the authors present a protocol combining NMR, computational and biophysical methods for the structural characterization of large dynamic protein complexes and show that TF forms a symmetric head-to-tail dimer.

    • Leonor Morgado
    • , Björn M. Burmann
    •  & Sebastian Hiller

  • Article
    | Open Access

    Changes in chromatin structure have been linked to organismal ageing. Here the authors show that altered histone expression and mitochondrial stress during C. elegans development result in chromatin changes and a cytosolic stress response that affects organismal longevity, and depends on HSF-1 and the chromatin remodeller, ISW-1.

    • Olli Matilainen
    • , Maroun S. Bou Sleiman
    •  & Johan Auwerx

  • Article
    | Open Access

    Hsp70s are highly conserved molecular chaperones that play multiple essential roles in maintaining cellular protein homeostasis. Here, the authors provide structural evidence for active substrate release by Hsp70s upon ATP binding and provide insight into the molecular mechanism of ATP-driven Hsp70 chaperone activity.

    • Jiao Yang
    • , Yinong Zong
    •  & Qinglian Liu

  • Article
    | Open Access

    The yeast Hsp70 homolog Ssb is a chaperone that binds translating ribosomes where it is thought to function primarily by promoting nascent peptide folding. Here the authors find that the ribosome biogenesis defect associated with the loss of Ssb is attributable to a specific disruption in TORC1 signaling rather than defects in ribosomal protein folding.

    • Kaivalya Mudholkar
    • , Edith Fitzke
    •  & Sabine Rospert

  • Article
    | Open Access

    Proteins fold under mechanical force during co-translational folding at the ribosome. Here, the authors use single molecule magnetic tweezers to study the influence of chaperones on protein folding and show that the ribosomal chaperone trigger factor acts as a mechanical foldase by promoting protein folding under force.

    • Shubhasis Haldar
    • , Rafael Tapia-Rojo
    •  & Julio M. Fernandez

  • Article
    | Open Access

    The F508 deletion (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) is the most common CF causing mutation. Here the authors show that cytosolic chaperones shift the F508del channel conformation to the native fold by kinetic and thermodynamic remodelling of the gating energetics towards that of wild-type CTFR.

    • Miklos Bagdany
    • , Guido Veit
    •  & Gergely L. Lukacs

  • Article
    | Open Access

    TDP-43 aggregation is linked to various diseases including amyotrophic lateral sclerosis. Here the authors show that acetylation of the protein triggers TDP-43 pathology in cultured cells and mouse skeletal muscle, which can be cleared through an HSF1-dependent chaperone mechanism that disaggregates the protein.

    • Ping Wang
    • , Connor M. Wander
    •  & Todd J. Cohen

  • Article
    | Open Access

    In the prevailing model for assisted protein folding, chaperonins act passively by preventing protein aggregation. Here, the authors use single-molecule fluorescence measurements and cryo-electron microscopy and show that theE. coliGroELS chaperonin system also has an active role in folding the endogenous bacterial protein PepQ.

    • Jeremy Weaver
    • , Mengqiu Jiang
    •  & Hays S. Rye

  • Article
    | Open Access

    The eukaryotic heat shock protein 90 (Hsp90) undergoes an ATP-dependent conformational cycle that is influenced by posttranslational modifications and co-chaperones. Here, the authors show that the yeast co-chaperone Hch1 can be functionally substituted by site-specific phosphorylation in human Hsp90.

    • Abbey D. Zuehlke
    • , Michael Reidy
    •  & Len Neckers

  • Article
    | Open Access

    Acl4 is a dedicated assembly chaperone for ribosomal protein RpL4 that recognizes RpL4 in the cytoplasm to facilitate its nuclear import. Here the authors reveal the mechanism whereby Acl4 recognizes RpL4 and functions to protect it from Tom1-mediated degradation until RpL4 incorporation into the maturing 60S pre-ribosomal subunit.

    • Ferdinand M. Huber
    •  & André Hoelz

  • Article
    | Open Access

    The correct folding of proteins often requires the intervention molecular chaperones, which can occur co-translationally. Here the authors identify elements of yeast Ssb (Hsp70) that mediate ribosomal binding, and suggest a mechanism that directs efficient interaction of Ssb with the nascent chain.

    • Marie A. Hanebuth
    • , Roman Kityk
    •  & Elke Deuerling

  • Article
    | Open Access

    Small heat shock proteins (sHsps) contribute to cellular recovery and survival following stress causing elevated levels of misfolded or unfolded proteins. Here the authors demonstrate that sHsps function by maintaining aggregating proteins in close-to-native conformations to facilitate chaperone-mediated refolding.

    • Sophia Ungelenk
    • , Fatemeh Moayed
    •  & Bernd Bukau

  • Article
    | Open Access

    Pluripotent stem cells are thought to require a highly active proteostatic machinery. Here, the authors show that CCT8, a subunit of the proteostatic chaperonin complex, is increased in pluripotent stem cells, and that overexpression of CCT8 in worms increases cellular proteostasis and organismal longevity.

    • Alireza Noormohammadi
    • , Amirabbas Khodakarami
    •  & David Vilchez

  • Article
    | Open Access

    Some bacterial toxin-antitoxin systems consist of a labile antitoxin that inhibits a toxin, and a chaperone that stabilizes the antitoxin. Here, Bordes et al. identify a sequence within the antitoxin to which the chaperone binds and which can be transferred to other proteins to make them chaperone-dependent.

    • Patricia Bordes
    • , Ambre Julie Sala
    •  & Pierre Genevaux

  • Article
    | Open Access

    The chaperone Hsp70 has a dual role, promoting both protein refolding and protein degradation. Seo and Park et al. show that Hsp70 acetylation enhances protein refolding after stress, and that subsequent deacetylation progressively promotes ubiquitin ligase binding and protein degradation.

    • Ji Hae Seo
    • , Ji-Hyeon Park
    •  & Kyu-Won Kim

  • Article
    | Open Access

    Building crystal structures into the electron density is an important step in protein structure solution. Here, the authors recruit online game players, students, and experienced crystallographers to compete in a competition to solve a new structure, and find that crowdsourcing model-building works.

    • Scott Horowitz
    • , Brian Koepnick
    •  & James C. A. Bardwell

  • Article
    | Open Access

    Hsp90 is required for the folding, stability and activity of several drivers of oncogenesis. Here the authors show that Folliculin-interacting proteins (FNIP) 1 and 2, whose expression correlates with the cellular response to Hsp90 inhibitors, are co-chaperones of Hsp90 that function by inhibiting its ATPase activity.

    • Mark R. Woodford
    • , Diana M. Dunn
    •  & Mehdi Mollapour

  • Article
    | Open Access

    Eukaryotic ribosome biogenesis involves a large number of maturations factors which are responsible for the stepwise assembly of the ribosomal subunits. Here the authors use an array of biochemical and structural biology methods to investigate the function of the UtpA and UtpB complexes as part of the small subunit processome.

    • Mirjam Hunziker
    • , Jonas Barandun
    •  & Sebastian Klinge

  • Article
    | Open Access

    Mutations in pendrin, a plasma membrane transporter, lead to Pendred syndrome, which is associated with hearing loss. Here, Jung et al. show that cell-surface expression of a mutated form of pendrin can be restored by blocking ER-to-Golgi traffic and triggering a DNAJC14 dependent unconventional secretion pathway.

    • Jinsei Jung
    • , Jiyoon Kim
    •  & Min Goo Lee

  • Article
    | Open Access

    Peter's Anomaly is a developmental disorder of the eye and has been linked to mutations in a range of genes, including the transcription factor FOXE3. Here the authors use next-generation RNA sequencing and mass spectrometry to identify an autophagy-associated protein, DNAJB1 as the transcriptional target of FOXE3.

    • Shahid Y. Khan
    • , Shivakumar Vasanth
    •  & S. Amer Riazuddin

  • Article
    | Open Access

    Molecular chaperones are recognized to interfere with protein aggregation, yet the underlying mechanisms are largely unknown. Here, the authors develop a kinetic model that reveals the variety of distinct microscopic mechanisms through which molecular chaperones act to suppress amyloid formation.

    • Paolo Arosio
    • , Thomas C. T. Michaels
    •  & Tuomas P. J. Knowles

  • Article
    | Open Access

    Under stress conditions the molecular chaperone Hsp33 is activated to process unfolded proteins. Here, the authors use in vivo and in vitro crosslinking and 19F-NMR to elucidate the binding site for misfolded proteins and are able to propose a model for its mechanism of action.

    • Bastian Groitl
    • , Scott Horowitz
    •  & Ursula Jakob

  • Article
    | Open Access

    Hsp70 chaperones are essential for cellular proteostasis, and their function depends on allosteric communication between their nucleotide- and substrate-binding domains. Here, Kityk et al.provide a mechanical model of allostery and demonstrate that ATP-induced substrate release is more important for chaperone activity than substrate-stimulated ATP hydrolysis.

    • Roman Kityk
    • , Markus Vogel
    •  & Matthias P. Mayer

  • Article
    | Open Access

    The synthesis of ribosomes requires the orderly assembly of many proteins and large RNA molecules, a process that involves several assembly factors. Here the authors show that dedicated chaperones capture the N termini of specific nascent ribosomal proteins to promote folding and assembly into maturing ribosomes.

    • Patrick Pausch
    • , Ujjwala Singh
    •  & Dieter Kressler

  • Article
    | Open Access

    The chaperones Hsp70 and Hsp90 are physically linked via the cochaperone Sti1/Hop, that has two binding sites for Hsp70. Here, Röhl et al.show that binding of Hsp90 changes the conformation of Sti1/Hop and determines to which site Hsp70 binds, perhaps facilitating transfer of client proteins from Hsp70 to Hsp90.

    • Alina Röhl
    • , Daniela Wengler
    •  & Johannes Buchner

  • Article
    | Open Access

    Heat shock induces proteotoxic stress, and the cellular response is mediated by heat-shock factor 1 (HSF1). Here, Tan et al.show that following heat shock, mitochondrial SSBP1 translocates to the nucleus and binds HSF1 to enhance the expression of chaperones and support the maintenance of mitochondrial function.

    • Ke Tan
    • , Mitsuaki Fujimoto
    •  & Akira Nakai

  • Article |

    Acyldepsipeptides are natural antibiotics that function by activating the ClpP protease and deregulating proteolysis. Here, Gersch et al.show that acyldepsipeptides not only increase access to the active sites but also exert conformational control, thereby allosterically stimulating ClpP catalysis.

    • Malte Gersch
    • , Kirsten Famulla
    •  & Stephan A. Sieber

  • Article |

    The bacterial Hsp70 chaperone system consists of DnaJ, DnaK and GrpE. To understand how these chaperones cooperate, Nunes et al. monitor refolding immunoglobulin domains using single-molecule force microscopy to demonstrate that the ‘holdase’ DnaJ can show foldase activity and suggest that GrpE can facilitate substrate release from DnaK.

    • João M. Nunes
    • , Manajit Mayer-Hartl
    •  & Daniel J. Müller

  • Article
    | Open Access

    Hypochlorous acid generated by neutrophils acts as a potent antibacterial agent. Müller et al. now show that this oxidant directly activates a protective counter-response in E. coli by N-chlorinating the protein RidA and converting it into an effective protein chaperone.

    • Alexandra Müller
    • , Sina Langklotz
    •  & Lars Ingo Ole Leichert

  • Article |

    While N-terminal acetylation has been shown to regulate the function or stability of a limited number of specific proteins, Holmes et al.report that global loss of this modification results in widespread protein misfolding, and show that the resulting stress response contributes to the suppression of a yeast prion phenotype.

    • William M. Holmes
    • , Brian K. Mannakee
    •  & Tricia R. Serio

  • Article |

    The activity of heat shock proteins (Hsp) is modified by binding to cochaperones. Here, the authors develop a four-colour FRET system to show that cochaperone p23 binding to Hsp90 strengthens the ATP-dependent directionality, thus validating their approach for the study of other multicomponent protein machines.

    • C. Ratzke
    • , B. Hellenkamp
    •  & T. Hugel

  • Article |

    Tumour cells utilize a pool of the molecular chaperone heat shock protein 90 to ensure correct protein folding in mitochondria. Here, the authors demonstrate that mitochondrial heat shock protein 90 regulates the folding of a subunit of the electron transport chain and that this can contribute to tumorigenesis.

    • Young Chan Chae
    • , Alessia Angelin
    •  & Dario C. Altieri

  • Article |

    The proteome of the malarial parasite Plasmodium falciparum has an overabundance of aggregation-prone asparagine repeat-containing proteins. Muralidharan et al. show that PlasmodiumHsp110 protein potently prevents aggregation of asparagine-rich proteins, thereby allowing the parasite to survive febrile episodes.

    • Vasant Muralidharan
    • , Anna Oksman
    •  & Daniel E. Goldberg

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