Chaperones articles within Nature Communications

Featured

  • 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

  • Article
    | Open Access

    The AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis that initiates cytoplasmic maturation of the large subunit. Here the authors report the structure of Drg1 in complex with its specific inhibitor diazaborine and provide insight into the mechanism of inhibition and specificity of this class of inhibitors.

    • Michael Prattes
    • , Irina Grishkovskaya
    •  & Helmut Bergler

  • Article
    | Open Access

    Structural insights into the small heat shock proteins (sHsps) complexes with their substrates are sparse. Here, cryo-EM structure of a plastid sHsp, Hsp21, in complex with a bona fide substrate 1-deoxy-D-xylulose 5-phosphate synthase (DXPS), suggests the anti-aggregation mechanism employed by sHsps.

    • Chuanyang Yu
    • , Stephen King Pong Leung
    •  & Wilson Chun Yu Lau

  • Article
    | Open Access

    The ER chaperone BiP is critical for the unfolded protein response and tightly regulated through reversible AMPylation by FICD, but the structural basis is unknown. Here the authors use thiol-reactive nucleotide derivatives to stabilize the transient FICD:BiP complex and determine its crystal structure.

    • Joel Fauser
    • , Burak Gulen
    •  & Aymelt Itzen

  • Article
    | Open Access

    The Hsp70/Hsp40 system plays an important role in maintaining cellular proteostasis but so far it is not well understood how Hsp70 proteins are recruited to specific Hsp40 co-chaperones. Here, the authors combine biochemical and biophysical approaches to characterise the oligomeric mammalian Hsp40 DnaJB8. They identify an intra-oligomer DnaJB8 interaction between the N-terminal J-Domain and the C-terminal domain that occludes the J-Domain surface that binds Hsp70 and propose a model for DnaJB8-Hsp70 recruitment.

    • Bryan D. Ryder
    • , Irina Matlahov
    •  & Lukasz A. Joachimiak

  • Article
    | Open Access

    Spy is an ATP independent chaperone that can act as both a holdase and a foldase towards topologically simple substrates. Assessing the interaction of Spy and apoflavodoxin, a complex client, the authors show that Spy’s activity is substrate specific. Spy binds partially unfolded states of apoflavodoxin tightly, which limits the possibility of folding and converts Spy to a pure holdase.

    • Rishav Mitra
    • , Varun V. Gadkari
    •  & James C. A. Bardwell

  • Article
    | Open Access

    p23 is a co-chaperone of Hsp90 but its mode of action is mechanistically not well understood. Here, the authors combine in vitro and yeast in vivo assays, biochemical measurements and NMR experiments to characterize p23 and identify two conserved helical elements in the intrinsically disordered C-terminal tail of p23 that together with the folded domain of p23 regulate the Hsp90 ATPase activity and affect the binding and maturation of Hsp90 clients.

    • Maximilian M. Biebl
    • , Abraham Lopez
    •  & Johannes Buchner

  • Article
    | Open Access

    The guided entry of tail-anchored proteins (GET) pathway assists in the delivery of such proteins to the ER. Here, the authors reveal that the pathway components Get4/5 probe a region near the ribosomal exit tunnel. Upon emergence of a client protein, Get4/5 recruits Sgt2 and initiates the targeting phase of the pathway.

    • Ying Zhang
    • , Evelina De Laurentiis
    •  & Sabine Rospert

  • Article
    | Open Access

    Existing methods for inflicting cellular heat shock are limited by the time delay in achieving the desired temperature and the spatial precision that can be achieved. Here the authors report a method to induce focused thermal protein damage using plasmonic silver nanoparticles.

    • Martin Mistrik
    • , Zdenek Skrott
    •  & Jiri Bartek

  • Article
    | Open Access

    ClpXP is the main ATP-dependent proteolytic complex in bacteria, is essential for maintaining cellular protein homeostasis and is also critical for bacterial pathogenesis. Here, the authors establish a functional link between ClpXP and trigger actor, a chaperone involved in the early stages of protein folding.

    • Kamran Rizzolo
    • , Angela Yeou Hsiung Yu
    •  & Walid A. Houry

  • Article
    | Open Access

    Most mitochondrial proteins are imported from the cytosol and must fold in the mitochondria. Here, the authors show that the mitochondrial protease LONP1 plays a critical role in the mtHSP70 chaperone system independently of its protease activity.

    • Chun-Shik Shin
    • , Shuxia Meng
    •  & David C. Chan

  • Article
    | Open Access

    Identifying factors that enable cells to induce a potent stress response to amyloid-like aggregation can provide further insight into the mechanism of stress regulation. Here, the authors express polyglutamine-expanded Huntingtin as a model disease protein in yeast cells and perform a genetic screen for chaperone factors that allow yeast cells to activate a potent stress response. They identify Sis1, an essential Hsp40 co-chaperone of Hsp70, as a critical sensor of proteotoxic stress and further show that both Sis1 and its mammalian homolog DnaJB6 regulate the magnitude of the cellular heat stress response, indicating that this mechanism is conserved.

    • Courtney L. Klaips
    • , Michael H. M. Gropp
    •  & F. Ulrich Hartl

  • Article
    | Open Access

    Biochemistry combined with biophysical measurements and mathematical modeling offer insight into the mechanism by which the cotranslational chaperone, nascent polypeptide-associated complex (NAC), modulates substrate selection by signal recognition particle (SRP) and reduces aberrant, nonspecific targeting of ribosomes to the ER.

    • Hao-Hsuan Hsieh
    • , Jae Ho Lee
    •  & Shu-ou Shan

  • Article
    | Open Access

    Changes in osmotic homeostasis alter metabolites and therefore chemical milieu of the cells. Here, the authors show that altering metabolites in E. coli also change the cellular capacity for buffering mutations that impair protein folding and influences proteostasis irrespective of molecular chaperones

    • Kanika Verma
    • , Kanika Saxena
    •  & Kausik Chakraborty

  • Article
    | Open Access

    The chaperone SurA is involved in outer membrane protein (OMP) biogenesis in Gram-negative bacteria, but its mechanism of action is not fully understood. Combining mass spectrometric, biophysical and computational approaches, the authors here show how the conformational dynamics of SurA facilitate OMP binding.

    • Antonio N. Calabrese
    • , Bob Schiffrin
    •  & Sheena E. Radford

  • Article
    | Open Access

    The ribosome-associated complex (RAC), which contains the Hsp40 protein Zuo1 and the non-canonical Hsp70 protein Ssz1 forms a chaperone triad with the fungal-specific Hsp70 protein Ssb. Here the authors combine X-ray crystallography, crosslinking and biochemical experiments and present the structure of the Zuo1 N-terminus bound to Ssz1 and demonstrate that Ssz1 is an active chaperone for nascent chains.

    • Ying Zhang
    • , Genís Valentín Gesé
    •  & Irmgard Sinning

  • Article
    | Open Access

    The chaperone Hsp90 uses the free energy from ATP hydrolysis to control the folding of client proteins in eukaryotic cells. Here the authors provide mechanistic insights into how its catalytic activity is coupled to conformational changes by combining large-scale molecular simulations with NMR, FRET and SAXS experiments.

    • Sophie L. Mader
    • , Abraham Lopez
    •  & Ville R. I. Kaila

  • Article
    | Open Access

    Methylation of a lysine residue in Hsp90 is a recently discovered post-translational modification but the mechanistic effects of this modification have remained unknown so far. Here the authors combine biochemical and biophysical approaches, molecular dynamics (MD) simulations and functional experiments with yeast and show that this lysine is a switch point, which specifically modulates conserved Hsp90 functions including co-chaperone regulation and client activation.

    • Alexandra Rehn
    • , Jannis Lawatscheck
    •  & Johannes Buchner

  • Article
    | Open Access

    Tau fibril formation is a hallmark of Alzheimer’s disease. Here the authors reveal an aggregation-dependent protein interaction pattern of Tau and further show that π-stacking of the arginine side-chains drives aberrant protein binding to Tau fibrils.

    • Luca Ferrari
    • , Riccardo Stucchi
    •  & Stefan G. D. Rüdiger

  • Article
    | Open Access

    Quantitative profiling of small molecule-protein binding in cells can aid basic biochemical research and drug discovery. Here, the authors develop the Heat Shock Protein Inhibition Protein Stability Assay (HIPStA) as a high-throughput method to assess cellular target engagement and identify new drug targets.

    • Kelvin F. Cho
    • , Taylur P. Ma
    •  & Robert A. Blake

  • Article
    | Open Access

    Transcription initiation involves the coordinated assembly and activity of large multimeric complexes. Here the authors report on the chaperone-mediated ordered assembly of the SAGA and NuA4 transcription co-activator complexes in fission yeast, providing insight into the de novo assembly of transcriptional complexes and the contribution of dedicated chaperones to this process.

    • Alberto Elías-Villalobos
    • , Damien Toullec
    •  & Dominique Helmlinger

  • Article
    | Open Access

    The sequestration of misfolded proteins into large assemblies by sequestrases is now considered as the third pillar in protein quality control besides chaperones and proteases. Here the authors characterise the functions of the sequestrases Hsp42 and Btn2 in the proteostasis network of S. cerevisiae and find that they protect cells from too exhaustive depletion of the Hsp70 system.

    • Chi-ting Ho
    • , Tomas Grousl
    •  & Axel Mogk

  • Article
    | Open Access

    Spy is an ATP independent chaperone that allows folding of its client protein Im7 while continuously bound to Spy. Here the authors employ kinetics measurements to study the folding of another Spy client protein SH3 and find that Spy’s ability to allow a client to fold while bound is inversely related to how strongly it interacts with that client.

    • Kevin Wu
    • , Frederick Stull
    •  & James C. A. Bardwell

  • Article
    | Open Access

    Myosin, a motor protein essential for intracellular transport to muscle contraction, requires a chaperone UNC-45 for folding and assembly. Here authors use in vitro reconstitution and structural biology to characterize the interplay between UNC-45 and muscle myosin MHC-B.

    • Doris Hellerschmied
    • , Anita Lehner
    •  & Tim Clausen

  • Article
    | Open Access

    It is unclear how unassembled secretory pathway proteins are discriminated from misfolded ones. Here the authors combine biophysical and cellular experiments to study the folding of heterodimeric interleukin 23 and describe how ER chaperones recognize unassembled proteins and aid their assembly into protein complexes while preventing the premature degradation of unassembled units.

    • Susanne Meier
    • , Sina Bohnacker
    •  & Matthias J. Feige

  • Article
    | Open Access

    S. cerevisiae encodes two Hsp90 isoforms, the constitutively expressed Hsc82 and stress-inducible Hsp82 that are 97% identical. Here, the authors combine a range of biophysical methods and show that they differ in their enzymatic properties, resilience to stress and client range, which suggests that they evolved to provide fine-tuned chaperone assistance under physiological and stress conditions.

    • Hannah Girstmair
    • , Franziska Tippel
    •  & Johannes Buchner

  • Article
    | Open Access

    Hsp chaperones stabilize the inactive conformation of androgen receptor (AR) and are released upon hormone-induced AR activation. Here, the authors locate the Hsp binding region on AR, and show that Hsp70 reduces AR aggregation and promotes AR degradation in cellular and mouse models of a neuromuscular disorder.

    • Bahareh Eftekharzadeh
    • , Varuna C. Banduseela
    •  & Xavier Salvatella

  • Article
    | Open Access

    β-propeller domains are an important class of folding substrates for the eukaryotic cytosolic chaperonin CTT. Here the authors find that CTT contributes to the folding and assembly of two β-propeller proteins from mTOR complexes, mLST8 and Raptor, and determine the 4.0 Å cryoEM structure of a human mLST8-CCT intermediate that shows mLST8 in a near-native state.

    • Jorge Cuéllar
    • , W. Grant Ludlam
    •  & José M. Valpuesta

  • Article
    | Open Access

    The small heat-shock protein HSP27 occurs predominantly in oligomeric forms, which makes its structural characterisation challenging. Here the authors employ CPMG and high-pressure NMR with native mass spectrometry and biophysical assays to show that the active monomeric form of HSP27 is substantially disordered and highly chaperone-active.

    • T. Reid Alderson
    • , Julien Roche
    •  & Andrew J. Baldwin

  • Article
    | Open Access

    SecB homologs can be associated with stress-responsive type II toxin–antitoxin (TA) systems and form tripartite toxin-antitoxin-chaperone systems (TAC). Here the authors provide structural insights into TACs by presenting the crystal structure of the M. tuberculosis TA-associated SecB chaperone in complex with the C-terminal ChAD (chaperone addiction) extension of the antitoxin HigA1.

    • Valérie Guillet
    • , Patricia Bordes
    •  & Lionel Mourey

  • Article
    | Open Access

    The role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in maintenance of protein folding homeostasis inside the ER has remained unclear. Here the authors determine the structure of the complex between MANF and the ER-localized chaperone BiP and provide evidence that MANF serves as an anti-nucleotide exchange factor for BiP.

    • Yahui Yan
    • , Claudia Rato
    •  & David Ron

  • Article
    | Open Access

    BAG3 is a Hsp70 co-chaperone that is highly expressed in muscles. Here the authors show that several myofibrillar myopathy causing BAG3 mutations are not impaired in Hsp70 binding, but rather impair the ADP-ATP exchange step of the Hsp70 cycle, causing the aggregation of BAG3, Hsp70 and Hsp70 clients and leading to a collapse of protein homeostasis.

    • Melanie Meister-Broekema
    • , Rebecca Freilich
    •  & Harm H. Kampinga

  • Article
    | Open Access

    The chaperone Hsp90 plays a key role in maintaining cellular homeostasis. Here the authors provide structural insights into substrate recognition and the pro-folding mechanism of Hsp90/co-chaperone complexes by studying the complex of Hsp90 with its co-chaperone FKBP51 and the substrate Tau bound Hsp90/FKBP51 ternary complex using a NMR based integrative approach.

    • Javier Oroz
    • , Bliss J. Chang
    •  & Markus Zweckstetter

  • Article
    | Open Access

    Many bacterial proteins exhibit spatially defined localization important for function. Here the authors show that the polar localization of Shigella IpaC type III secretion substrate is mediated by its interaction with the DnaK chaperone and occlusion by the bacterial nucleoid.

    • Clémence Collet
    • , Jenny-Lee Thomassin
    •  & Guy Tran Van Nhieu

  • Article
    | Open Access

    The heat shock protein 90 (Hsp90) chaperone undergoes large conformational changes during its functional cycle. Here the authors combine in vivo, biochemical, biophysical and computational approaches and provide insights into the allosteric regulation of Hsp90 by identifying and characterizing a switch point in the Hsp90 middle domain.

    • Daniel Andreas Rutz
    • , Qi Luo
    •  & Johannes Buchner

  • Article
    | Open Access

    An integrated network of chaperones and protein degradation machineries called the proteostasis network (PN) is required to maintain protein homeostasis. Here the authors show that one of the components of the PN, the chaperonin TRiC, interacts with the core transcription-coupled nucleotide excision repair protein CSA to ensure its assembly into the CRLCSA complex.

    • Alex Pines
    • , Madelon Dijk
    •  & Haico van Attikum

  • Article
    | Open Access

    Aggregation is sequence-specific and nucleated by short aggregating protein segments (APR). Here authors use a multidisciplinary approach to show that in E.coli some frequently occurring APRs lead to protein aggregation and ultimately bacterial cell death, which could serve as antibacterial strategy.

    • Ladan Khodaparast
    • , Laleh Khodaparast
    •  & Joost Schymkowitz

  • Article
    | Open Access

    The U-box ubiquitin ligase UFD-2 is one of the most abundant components of the ubiquitin proteasome system in muscle cells. Here the authors perform in vitro and in vivo experiments and show that UFD-2 has E3 ligase activity and that it ubiquitinates unfolded myosin using the C. elegans myosin chaperone UNC-45 as an adaptor protein.

    • Doris Hellerschmied
    • , Max Roessler
    •  & Tim Clausen

Browse broader subjects

Browse Chaperones across other nature.com journals