Chaperones articles within Nature Communications

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  • Article
    | Open Access

    Here the authors discover a dedicated ribosome-associated chaperone, Chp1, that assists in the challenging biogenesis of eukaryotic translation elongation factor 1A (eEF1A) by cotranslationally stabilizing the growing GTPase domain of eEF1A.

    • Melania Minoia
    • , Jany Quintana-Cordero
    •  & Claes Andréasson
  • Article
    | Open Access

    Proper cellular proteostasis requires a network of the chaperonin TRiC/CCT with cochaperones prefoldin (PFD) and phosducin-like proteins (PhLPs) to facilitate the folding of essential eukaryotic proteins. Here, the authors characterized the ATP-driven cycle of TRiC-PFD-PhLP2A interaction using cryoEM and biochemical analyses.

    • Junsun Park
    • , Hyunmin Kim
    •  & Soung-Hun Roh
  • Article
    | Open Access

    Here, using single molecule FRET, the unfolding and folding of a discontinuous two-domain protein was studied. The authors find that a dynamic, intermediate population entropically limits the rate of folding while the order of domain folding is kept in a slow-folding mutant.

    • Ganesh Agam
    • , Anders Barth
    •  & Don C. Lamb
  • Article
    | Open Access

    The precise role of cochaperones and ATP hydrolysis in driving Hsp90’s chaperone cycle is largely unclear. Here, the authors use single-molecule FRET to show that several cochaperones are necessary to establish directionality in Hsp90’s conformational cycle.

    • Leonie Vollmar
    • , Julia Schimpf
    •  & Thorsten Hugel
  • Article
    | Open Access

    Newly synthesized tail-anchored membrane proteins (TAs) are relayed in a chaperone triad, Hsp70, Sgt2, and Get3, for delivery to the endoplasmic reticulum. Here, the authors show how the conformational dynamics of the cochaperone Sgt2 generates a decision point to enable efficient and selective TA targeting.

    • Hyunju Cho
    • , Yumeng Liu
    •  & Shu-ou Shan
  • Comment
    | Open Access

    Molecular chaperones establish essential protein-protein interaction networks. Modified versions of these assemblies are generally enriched in certain maladies. A study published in Nature Communications used epichaperomics to identify unique changes occurring in chaperone-formed protein networks during mitosis in cancer cells.

    • Mark R. Woodford
    • , Dimitra Bourboulia
    •  & Mehdi Mollapour
  • Article
    | Open Access

    Epichaperomics allow the study of protein-protein interactions and their alterations, but probes have been limited to capturing HSP90 epichaperomes. Here, the authors introduce and validate a toolset of HSP70 epichaperome ligands, and use them in epichaperomics to identify a mechanism with which cancer cells can enhance the fitness of mitotic protein networks.

    • Anna Rodina
    • , Chao Xu
    •  & Gabriela Chiosis
  • Article
    | Open Access

    How soluble misfolded proteins can bypass chaperones is unknown. Utilizing a meta-analysis, multi-scale modelling, and new experimental data it is found that this phenomena is common and arises from misfolded states that are native-like and long-lived due to protein self-entanglements.

    • Ritaban Halder
    • , Daniel A. Nissley
    •  & Edward P. O’Brien
  • Article
    | Open Access

    Importins are known to facilitate nucleocytoplasmic transport and cytoplasmic chaperoning of some proteins. Here, the authors uncover that these proteins also act as co-translational chaperones for specific sets of proteins, for example ribonucleic acid binding factors.

    • Maximilian Seidel
    • , Natalie Romanov
    •  & Martin Beck
  • Article
    | Open Access

    Hsp110 chaperones play important roles in protein homeostasis in eukaryotes. Here, the authors identify a small compound that inhibits fungal Hsp110s as well as the growth and viability of the pathogenic fungus Candida albicans, supporting Hsp110s as targets for development of new antifungal drugs.

    • Liqing Hu
    • , Cancan Sun
    •  & Qinglian Liu
  • Article
    | Open Access

    A complete understanding of the role of ATP hydrolysis in Hsp90 function is elusive. Here, the authors show that ATP hydrolysis, but not binding, is dispensable for essential or specialized Hsp90 functions in vivo, shedding new light on this mystery.

    • Michael Reidy
    • , Kevin Garzillo
    •  & Daniel C. Masison
  • Article
    | Open Access

    PP5 requires the molecular chaperone Hsp90 to dephosphorylate CRaf kinase and the Hsp90 cochaperone Cdc37. Here, authors show how Hsp90 acts as a platform to allow for targeted dephosphorylation by PP5.

    • Maru Jaime-Garza
    • , Carlos A. Nowotny
    •  & David A. Agard
  • Article
    | Open Access

    The mitochondrial ATP synthase produces the bulk of cellular ATP. Here, the authors report a function of the mitochondrial Hsp70 in the formation of the catalytical head and in its assembly with the peripheral stalk to form the mature ATP synthase.

    • Jiyao Song
    • , Liesa Steidle
    •  & Thomas Becker
  • Article
    | Open Access

    Binding to HSP90-CDC37 is essential for the activity of many protein kinases, but its function is unclear. Here, the authors show that HSP90-CDC37 provides a structural platform for the phosphatase PP5 to dephosphorylate a bound kinase, ‘factory resetting’ it prior to release.

    • Jasmeen Oberoi
    • , Xavi Aran Guiu
    •  & Laurence H. Pearl
  • Article
    | Open Access

    This study describes how p97Ufd1-Npl4 and the UBA-UBX protein Ubxn7 disassemble vertebrate replisomes during replication termination, and it provides novel insights into how p97 complexes assemble with UBA-UBX proteins on ubiquitylated substrates

    • Olga V. Kochenova
    • , Sirisha Mukkavalli
    •  & Johannes C. Walter
  • Article
    | Open Access

    The catalytic chaperone tapasin assists peptide loading onto MHC-I molecules for antigen presentation and immune recognition. Here, the authors present crystal structures that provide insights into the molecular mechanism of tapasin-mediated peptide exchange.

    • Jiansheng Jiang
    • , Daniel K. Taylor
    •  & Kannan Natarajan
  • Article
    | Open Access

    The immune system monitors the health status of cells by surveilling fragments of foreign molecules from invaders presented on MHC I complexes at the cell surface. Here, the authors investigate the sequence of events of MHC I assembly and quality control cycle.

    • Alexander Domnick
    • , Christian Winter
    •  & Robert Tampé
  • Article
    | Open Access

    Ayala Mariscal et al have identified and characterized the interface of pathogenic Huntingtin and the molecular chaperone DNAJB1. Histidine-244 of the C-terminal domain of DNAJB1 is a key residues for binding to the poly-proline region of HTT. This binding site is specific for the interaction with Huntingtin.

    • S. M. Ayala Mariscal
    • , M. L. Pigazzini
    •  & J. Kirstein
  • Article
    | Open Access

    Low solubility and stability of Escherichia coli produced single chain variable fragments (scFvs) restrict their applications. Here the authors report a 33-residue peptide tag which simultaneously increases the solubility and thermostability of multiple scFvs produced in Escherichia coli SHuffle strain.

    • Yang Wang
    • , Wenjie Yuan
    •  & Yong-Xiang Wang
  • Article
    | Open Access

    Here the authors describe mechanisms through which analogous LGMDD1 (Limb-Girdle Muscular Dystrophy Type D1) mutations affect Sis1 (a yeast functional homolog of human DNAJB6) chaperone activity and poison the function of wild-type protein; potentially uncovering a new therapeutic route to explore.

    • Ankan K. Bhadra
    • , Michael J. Rau
    •  & Heather L. True
  • Article
    | Open Access

    Using Guanidium HCl denatured glyceraldehyde 3-phosphate dehydrogenase (GAPDH), the authors provide in vitro evidence for the active involvement of the trigger factor (TF) in promoting the native folding of pre-unfolded client proteins, by preventing non-productive self-associations (misfolding) and by shielding oligomeric interfaces from aggregation.

    • Kevin Wu
    • , Thomas C. Minshull
    •  & James C. A. Bardwell
  • Article
    | Open Access

    Mitochondrial cytochrome c oxidase is a heme aa3-copper oxygen reductase. Here, authors report that metal center-specific metallochaperones form dynamic assemblies to control heme a biosynthesis and coordinate copper transfer to the copper sites.

    • Eva Nývltová
    • , Jonathan V. Dietz
    •  & Antoni Barrientos
  • Article
    | Open Access

    How ATP-independent chaperones release their clients without energy input remains enigmatic. Here the authors discover that chaperone Spy uses its long, disordered N terminus to facilitate client release through competitive, dynamic intramolecular interactions with Spy’s client binding surface.

    • Wei He
    • , Xinming Li
    •  & Shu Quan
  • Article
    | Open Access

    Proteomics can define features of proteome foldedness by assessing the reactivity of surface exposed amino acids. Here, the authors show that such exposure patterns yield insight to structural changes in chaperones as they bind to unfolded proteins in urea-denatured mammalian cell lysate.

    • Dezerae Cox
    • , Ching-Seng Ang
    •  & Danny M. Hatters
  • Article
    | Open Access

    Interstitial Lung Disease (ILD)-associated mutations in surfactant protein C (SP-C) render the protein prone to aggregation. Here, the authors reveal their impact on protein maturation, provide insights into recognition of aggregation prone regions by chaperones, and address the autosomal dominant nature of ILD mutants.

    • Kristine F. R. Pobre-Piza
    • , Melissa J. Mann
    •  & Linda M. Hendershot
  • Article
    | Open Access

    Tousled-like kinase 2 (TLK2) phosphorylates ASF1 histone chaperones to promote nucleosome assembly in S phase. Here, the authors show that TLK2 targets ASF1 by simulating its client protein histone H3, exploiting a primordial protein interaction surface for regulatory control.

    • Bertrand Simon
    • , Hua Jane Lou
    •  & David A. Calderwood
  • Article
    | Open Access

    Revealing mechanisms of complex protein machines requires simultaneous exploration of multiple structural coordinates. Here the authors report two-colour fluorescence microscopy combined with photoinduced electron transfer probes to simultaneously detect two structural coordinates in single protein molecules.

    • Jonathan Schubert
    • , Andrea Schulze
    •  & Hannes Neuweiler
  • Article
    | Open Access

    Small heat shock proteins (sHsps) form large spherical assemblies and their regulation is not well understood. Here, the authors provide insights into the mechanism of Hsp26 activation by characterising phospho-mimetic mutants of yeast Hsp26. They present cryo-EM structures of the wild-type Hsp26 40mer and its phospho-mimetic mutants that reveal the location of the thermosensor in the oligomer, and the authors also show that the thermosensor domain is targeted by phosphorylation, which relieves the intrinsic inhibition of chaperone activity.

    • Moritz Mühlhofer
    • , Carsten Peters
    •  & Johannes Buchner
  • Article
    | Open Access

    Molecular chaperones from the Hsp70 family can break up protein aggregates, including amyloids. Here, the authors utilize microfluidic diffusional sizing to assess the mechanism of α-synuclein (αS) disaggregation by the Hsc70–DnaJB1–Apg2 system, and show that single αS molecules are removed directly from the fibril ends.

    • Matthias M. Schneider
    • , Saurabh Gautam
    •  & Tuomas P. J. Knowles
  • Article
    | Open Access

    In vitro protein folding can often result in aggregation and low yields. Here the authors use nanoscale exoshells to improve soluble yield, functional yield and specific activity of folded proteins.

    • Samira Sadeghi
    • , Siddharth Deshpande
    •  & Chester L. Drum
  • Article
    | Open Access

    Here, the authors use in vivo site-specific crosslinking to provide molecular-level insight into how the fungal Hsp70 chaperone system — the Ssb:Ssz1:Zuo1 triad — assists the folding process for the nascent peptide chain emerging from the ribosome tunnel.

    • Kanghyun Lee
    • , Thomas Ziegelhoffer
    •  & Elizabeth A. Craig
  • Article
    | Open Access

    Protein binding by the Hsp70/J-domain protein (JDP) chaperones prevents aggregation of the client protein. Here, the authors show that DnaJC7 binds preferentially to natively folded wild-type tau, via a β-turn element in tau that contains the known amyloid motif, while aggregation-prone tau mutants are recognized with reduced affinity.

    • Zhiqiang Hou
    • , Pawel M. Wydorski
    •  & Lukasz A. Joachimiak
  • Article
    | Open Access

    Variants of the extracellular chaperone Clusterin are associated with Alzheimer’s disease (AD) and Clusterin levels are elevated in AD patient brains. Here, the authors show that Clusterin binds to oligomeric Tau, which enhances the seeding capacity of Tau aggregates upon cellular uptake. They also demonstrate that Tau/Clusterin complexes enter cells via the endosomal pathway, resulting in damage to endolysosomes and entry into the cytosol, where they induce the aggregation of endogenous, soluble Tau.

    • Patricia Yuste-Checa
    • , Victoria A. Trinkaus
    •  & F. Ulrich Hartl
  • Article
    | Open Access

    RPAP3 is a subunit of the R2TP complex, a co-chaperone of HSP90, with substrate proteins involved in transcription, ribosome biogenesis, DNA repair and cell growth. Here the authors report that deletion of Rpap3 abrogates cell proliferation and homeostasis in mouse intestine, partly through destabilization of PI3K-like kinases, while elevated RPAP3 levels in colorectal tumors are associated with poor prognosis.

    • Chloé Maurizy
    • , Claire Abeza
    •  & Bérengère Pradet-Balade