Protein aggregation articles within Nature Communications

Featured

  • Article
    | Open Access

    Detection of amyloid beta deposits is often performed with fluorescent compounds that bind plaques. Here the authors develop turn-on chemiluminescent probes that bind amyloid beta plaques in vivo, and amplify the signal via chemiluminescence resonance energy transfer to the plaque-binding fluorescent molecule CRANAD-3.

    • Jing Yang
    • , Wei Yin
    •  & Chongzhao Ran

  • Article
    | Open Access

    ALS is a neurodegenerative disease characterized by loss of motor neurons. Here, the authors showed that reduced levels of the VSP35 subunit in the retromer complex is a conserved ALS feature and identified a new lead compound increasing retromer stability ameliorating the disease phenotype.

    • Luca Muzio
    • , Riccardo Sirtori
    •  & Gianvito Martino

  • Article
    | Open Access

    Rift Valley fever virus (RVFV) can cause severe diseases in humans, including encephalitis. Here the authors show that NSs, the major virulence factor of RVFV, is an amyloidogenic protein forming fibrils in infected mouse brains and causing increased mortality in mice.

    • Psylvia Léger
    • , Eliana Nachman
    •  & Pierre-Yves Lozach

  • Article
    | Open Access

    Nonsense-mediated mRNA decay (NMD) is a translation-coupled process that eliminates mRNAs containing premature translation-termination codons. Here the authors identify a role for the NMD factor UPF1 in protein quality control, whereby truncated misfolded polypeptides are cleared through autophagy.

    • Yeonkyoung Park
    • , Joori Park
    •  & Yoon Ki Kim

  • Article
    | Open Access

    The unfolded protein response (UPR) is a stress response pathway implicated in numerous diseases and chemotherapy resistance. Here, the authors define the UPR regulon with a multi-omics strategy, uncovering changes to mitochondrial one-carbon metabolism and concomitant resistance to folate-based therapeutics.

    • Stefan Reich
    • , Chi D. L. Nguyen
    •  & Jan Medenbach

  • Article
    | Open Access

    Tau plays an important role in tauopathies and undergoes liquid-liquid phase separation (LLPS). The authors show that disease-related P301L mutant and phosphomimic (S199E/S202E/T205E) tau enhance LLPS in vitro at physiological levels, and using specific antibodies, that tau LLPS leads to pathological conformations such as N-terminal exposure and oligomeric species.

    • Nicholas M. Kanaan
    • , Chelsey Hamel
    •  & Benjamin Combs

  • Article
    | Open Access

    Protein aggregation remains a significant challenge for manufacturing of protein biopharmaceuticals. Here, the authors demonstrate the use of directed evolution and an assay for in vivo innate protein aggregation-propensity to generate aggregation-resistant scFv fragments.

    • Jessica S. Ebo
    • , Janet C. Saunders
    •  & David J. Brockwell

  • Article
    | Open Access

    Galectin-3 consists of an unstructured N-terminal domain (NTD) and a structured carbohydrate-recognition domain and agglutinates neutrophils and glycosylated molecules in the extracellular milieu. Here the authors combine biophysical and biochemical experiments with NMR measurements and show that the galectin-3 NTD undergoes liquid-liquid phase separation (LLPS) and agglutinates other molecules through this process.

    • Yi-Ping Chiu
    • , Yung-Chen Sun
    •  & Jie-rong Huang

  • Article
    | Open Access

    It is not yet clear how ubiquitously-expressed proteins can cause the selective degeneration of particular populations of neurons, such as in spinocerebellar ataxia type 17, SCA17, which results from a CAG trinucleotide repeat expansion in the ubiquitously expressed transcription factor TBP. Here, the authors show that mutant TBP suppresses the cerebellum-enriched transcription of Inpp5a and link altered levels of INPP5A to the selective degeneration of cerebellar neurons.

    • Qiong Liu
    • , Shanshan Huang
    •  & Shihua Li

  • 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

    Single-molecule in vitro assays require dedicated confocal microscopes equipped with fluorescence correlation spectroscopy (FCS) modules. Here the authors present a compact, cheap and open-source 3D-printed confocal microscope for single photon counting and FCS measurements, and use it to detect α-synuclein aggregation.

    • James W. P. Brown
    • , Arnaud Bauer
    •  & Yann Gambin

  • Article
    | Open Access

    While the cellular recycling process autophagy has been linked to aging, the impact of selective autophagy on lifespan remains unclear. Here Kumsta et al. show that the autophagy receptor p62/SQSTM1 is required for hormetic benefits and p62/SQSTM1 overexpression is sufficient to extend C. elegans lifespan and improve proteostasis.

    • Caroline Kumsta
    • , Jessica T. Chang
    •  & Malene Hansen

  • Article
    | Open Access

    Chiral inversion of amino acids is thought to modulate the structure and function of amyloid beta (Aβ) but these processes are poorly understood. Here, the authors develop an ion mobility-mass spectrometry based approach to study chirality-regulated structural features of Aβ fragments and their influence on receptor recognition.

    • Gongyu Li
    • , Kellen DeLaney
    •  & Lingjun Li

  • Article
    | Open Access

    Deposition of tau protein aggregates occurs during aging and Alzheimer disease. Here, the authors show that tau burden in the anterior-temporal memory network is associated with disrupted fMRI connectivity and functional isolation of the hippocampus from other memory network components.

    • Theresa M. Harrison
    • , Anne Maass
    •  & William J. Jagust

  • 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

    Processing bodies are membrane less organelles that contain enzymes involved in mRNA turnover, among them enhancer of decapping 3 (Edc3). Here the authors use solid- and solution-state NMR spectroscopy to characterize the structural organization and dynamics of Edc3 and find that its interactions with RNA and between the different Edc3 domains are largely preserved in the phase-separated state.

    • Reinier Damman
    • , Stefan Schütz
    •  & Marc Baldus

  • Article
    | Open Access

    Accumulation of abnormal tau protein drives neurodegeneration in Alzheimer’s disease and related dementia disorders. Here, the authors demonstrate the endoplasmic reticulum unfolded protein response mediator XBP-1 controls pathological tau accumulation and the resultant neurodegeneration in a transgenic C. elegans model.

    • Sarah M. Waldherr
    • , Timothy J. Strovas
    •  & Brian C. Kraemer

  • Article
    | Open Access

    The Src-homology 3 domain of phosphatidyl-inositol-3-kinase (PI3K-SH3) is a model system for studying amyloid fibril formation. Here the authors present the 3.4 Å cryo-EM structure of the PI3K-SH3 amyloid fibril, which allows them to rationalize the effects of mutations on the kinetics of fibril formation.

    • Christine Röder
    • , Nicola Vettore
    •  & Gunnar F. Schröder

  • Article
    | Open Access

    Proteins have been used in the synthesis of magnetic nanoparticles but issues with aggregation limit this application. Here, the authors report on the synthesis of coiled proteins that display the active loop of the natural proteins to avoid aggregation and investigate the application in nanoparticle synthesis.

    • Andrea E. Rawlings
    • , Lori A. Somner
    •  & Sarah S. Staniland

  • Article
    | Open Access

    Bacterial ClpB is a disaggregase that solubilizes protein aggregates. Here the authors present the 2.9 Å cryo-EM structure of a hyperactive variant of ClpB bound to the substrate casein in active translocation states and discuss its polypeptide translocation mechanism.

    • Alexandrea N. Rizo
    • , JiaBei Lin
    •  & Daniel R. Southworth

  • Article
    | Open Access

    Genes encoding protein complex subunits are often dispersed in the genome of eukaryotes, raising the question how these protein complexes assemble. Here, the authors provide evidence that mammalian nuclear transcription complexes are formed co-translationally to ensure specific and functional interactions.

    • Ivanka Kamenova
    • , Pooja Mukherjee
    •  & László Tora

  • Article
    | Open Access

    Prion-forming proteins have been found in animals, plants, fungi, and bacteria. Here, Nan et al. report that a baculovirus-encoded protein behaves as prion in a yeast system and forms aggregates at high multiplicity of infection in insect cells that affect baculovirus replication.

    • Hao Nan
    • , Hongying Chen
    •  & Xiaodong Xu

  • Article
    | Open Access

    Small molecule metabolites like phenylalanine can form amyloid-like structures but so far this has only been demonstrated in vitro. Here the authors generate a yeast in vivo model of adenine self-assembly and characterize the adenine assemblies in cells by indicative amyloid dye and anti-adenine assemblies antibodies.

    • Dana Laor
    • , Dorin Sade
    •  & Ehud Gazit

  • Article
    | Open Access

    Impaired kidney function can lead to an increase of β2-microglobulin (β2m) serum levels, which can cause β2m aggregation and amyloid fibril formation. Here the authors combine cryo-EM and magic angle spinning NMR measurements to determine the structure of a β2m fibril and they also present the low resolution model of a β2m fibril with a different morphology.

    • Matthew G. Iadanza
    • , Robert Silvers
    •  & Sheena E. Radford

  • Article
    | Open Access

    Manual sample deposition on a substrate can introduce artifacts in quantitative AFM measurements. Here the authors present a microfluidic spray device for reliable deposition of subpicoliter droplets which dry out in milliseconds after landing on the surface, thereby avoiding protein self-assembly.

    • Francesco Simone Ruggeri
    • , Jerome Charmet
    •  & Tuomas P. J. Knowles

  • Article
    | Open Access

    The phenol-soluble modulin PSMα3 secreted by Staphylococcus aureus forms cross-α amyloid-like fibrils. Here the authors reveal the amyloid polymorphism of PSMs by presenting the cross-β amyloid fibril structures of the biofilm-associated PSMα1 and PSMα4 and showing that truncated PSMα3 antibacterial peptides form distinct out-of-register β-sheets and a polymorph with a hexameric architecture of β-sheets.

    • Nir Salinas
    • , Jacques-Philippe Colletier
    •  & Meytal Landau

  • Article
    | Open Access

    Mutations in LRRK2 kinase are associated with Parkinson’s disease. Here the authors show that LRRK2 modulates propagation of α-synuclein, using rodent and C. elegans models, and show that this is dependent on phosphorylation of one of its substrates, RAB35.

    • Eun-Jin Bae
    • , Dong-Kyu Kim
    •  & Seung-Jae Lee

  • Article
    | Open Access

    The structures of amyloid fibres are currently primarily studied through solid state NMR and cryo-EM. Here the authors present a free-standing graphene support device that allows diffraction imaging of non-crystalline amyloid fibrils with single X-ray pulses from an X-ray free-electron laser.

    • Carolin Seuring
    • , Kartik Ayyer
    •  & Henry N. Chapman

  • Article
    | Open Access

    The aggregation prone D76N beta-2 microglobulin mutant causes systemic amyloidosis. Here the authors combine crystallography, solid-state NMR, and computational studies and show that the D76N mutation increases protein dynamics and destabilizes the outer strands, which leads to an exposure of amyloidogenic parts explaining its aggregation propensity.

    • Tanguy Le Marchand
    • , Matteo de Rosa
    •  & Stefano Ricagno

  • Article
    | Open Access

    Disruption of the ubiquitin proteasome system (UPS) is often associated with neurodegenerative diseases. Here the authors demonstrate the existence of a general mechanism of proteasomal impairment triggered by a specific protein oligomer structure, irrespective of its protein constituent.

    • Tiffany A. Thibaudeau
    • , Raymond T. Anderson
    •  & David M. Smith

  • 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

    Amyloid fibril structures can display polymorphism. Here the authors reveal the cryo-EM structures of several different fibril morphologies of a peptide derived from an amyloidogenic immunoglobulin light chain and present a mathematical analysis of physical factors that influence fibril polymorphism.

    • William Close
    • , Matthias Neumann
    •  & Marcus Fändrich

  • Article
    | Open Access

    The Alzheimer protein Tau interacts with biological membranes, but the role of these interactions in regulating Tau function in health and disease remains unexplored. Here, the authors report on the discovery and characterization of neurotoxic oligomeric protein/phospholipid complexes.

    • Nadine Ait-Bouziad
    • , Guohua Lv
    •  & Hilal A. Lashuel

  • Article
    | Open Access

    Aggregation of amyloidogenic peptides into fibrils and crystals has incidence in several amyloid-related diseases. Here, the authors investigate the origins of the fibril-to-crystal conversion in amyloidogenic hexapeptides pointing to the amyloid crystals as the ground state in the protein folding energy landscape.

    • Nicholas P. Reynolds
    • , Jozef Adamcik
    •  & Raffaele Mezzenga

  • Article
    | Open Access

    Prion diseases can be transmitted across species. Here the authors use solid-state NMR to study prion protein (PrP) amyloids from human, mouse and Syrian hamster and show that their structural differences are mainly governed by two residues, which helps to understand interspecies PrP propagation on a molecular level.

    • Theint Theint
    • , Philippe S. Nadaud
    •  & Christopher P. Jaroniec

  • Article
    | Open Access

    Seeding of amyloid beta from one brain region to another is thought to contribute to the progression of Alzheimer’s disease, although to date most studies have depended on inoculation of animals with exogenous amyloid. Here the authors describe a genetic seed and target system in Drosophila which may be useful for the mechanistic study of seeding of amyloid in vivo.

    • Ramona F. Sowade
    •  & Thomas R. Jahn

  • Article
    | Open Access

    Proteostasis is maintained through a number of molecular mechanisms, some of which function to protect the folded state of proteins. Here the authors demonstrate the use of TPE-MI in a fluorigenic dye assay for the quantitation of unfolded proteins that can be used to assess proteostasis on a cellular or proteome scale.

    • Moore Z. Chen
    • , Nagaraj S. Moily
    •  & Danny M. Hatters

  • 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

Browse broader subjects

Browse Protein aggregation across other nature.com journals