RETRACTED: Autoadaptive ER-Associated Degradation Defines a Preemptive Unfolded Protein Response Pathway

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Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2 ' 3 '-cyclic GMP-AMP (cGAMP)1-7. The indiscriminate activity of cGAS towards DNA d ...

DNA damage signaling following DNA double-strand breaks (DSBs) involves numerous regulating proteins, which dynamically recognize ('read') and alter ('write' or 'erase') histone post-translational modifications (PTMs). Among these PTMs, the ubiquitin syste ...

The 70 kDa heat shock protein (Hsp70) chaperones control protein homeostasis in all ATP-containing cellular compartments. J-domain proteins (JDPs) coevolved with Hsp70s to trigger ATP hydrolysis and catalytically upload various substrate polypeptides in ne ...

Cartilage homeostasis, crucial for musculoskeletal function, is orchestrated by interconnected biophysical cues. In healthy cartilage, repetitive compressive loading not only elicits a range of mechanical stimuli but also induces a gradual transient temper ...

Cells have evolved endocytic pathways to internalize different molecules, to regulate intra-cellular communication and their interaction with external environment. Pathogens have co-evolved with cells to exploit these processes for infections. In particula ...

The cellular protein levels are determined by protein synthesis and turnover rates. Two processes are involved in the proteome's turnover in proliferating cells: protein degradation and dilution. In theory, maintaining the cellular proteome concentration, ...

The Hsp70 cycle is a key element of protein homeostasis, which is essential to avoid protein aggregation and protein-related diseases. Despite many experimental observations of the interaction between Hsp70, its co-chaperone DnaJ and various substrates, li ...

Solving native structures of such large molecules, like biomolecules, is often challenging, particularly due to the potentially infinite number of non-covalent interactions with water. In this thesis, we report the use of cold ion gas-phase action spectros ...

Hsp60 chaperonins and their Hsp10 cofactors assist protein folding in all living cells, constituting the paradigmatic example of molecular chaperones. Despite extensive investigations of their structure and mechanism, crucial questions regarding how these ...

TAR DNA-binding protein with 43 kD (TDP-43) is a partially disordered protein that misfolds and accumulates in the brains of patients affected by several neurodegenerative diseases. TDP-43 oligomers have been reported to form due to aberrant misfolding or ...

Detailed understanding of the mechanism by which Hsp70 chaperones protect cells against protein aggregation is hampered by the lack of a comprehensive characterization of the aggregates, which are typically heterogeneous. Here we designed a reporter chaper ...

The J-domain proteins (JDP) form the largest protein family among cellular chaperones. In cooperation with the Hsp70 chaperone system, these co-chaperones orchestrate a plethora of distinct functions, including those that help maintain cellular proteostasi ...

Abnormal tau protein aggregates constitute a hallmark of Alzheimer's disease. The mechanisms underlying the initiation of tau aggregation in sporadic neurodegeneration remain unclear. Here we investigate whether a non-human prion can seed tau aggregation. ...

The sheer size of the protein sequence space is massive: a protein of 100 residues can have 20^100 possible sequence combinations; and knowing that this exceeds the number of atoms in the universe, the chance of randomly discovering a stable new sequence w ...

Increasing the protein production capacity of the PURE cell-free transcription-translation (TX-TL) system will be key to implementing complex synthetic biological circuits, and to establishing a fully self-regenerating system as a basis for the development ...

Synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy (MSA) are detrimental neurodegenerative diseases. Alpha-synuclein (aSyn), the main aggregating protein found in the pathological inclusions of these ailmen ...

Alteration to endoplasmic reticulum (ER) proteostasis is observed in a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteost ...

Life is a non-equilibrium phenomenon. Owing to their high free energy content, the macromolecules of life tend to spontaneously react with ambient oxygen and water and turn into more stable inorganic molecules. A similar thermodynamic picture applies to th ...

Continuous assessment of transferable forcefields for molecular simulations is essential to identify their weaknesses and direct improvement efforts. The latest efforts focused on better describing disordered proteins while retaining proper description of ...

Non-Syndromic Hereditary Hearing Loss (NSHHL) is a genetically heterogeneous sensory disorder with about 120 genes already associated. Through exome sequencing (ES) and data aggregation, we identified a family with six affected individuals and one unrelate ...

RETRACTED: Autoadaptive ER-Associated Degradation Defines a Preemptive Unfolded Protein Response Pathway

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The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation

A chemical biology approach to decipher chromatin ubiquitylation by RNF168

Autorepression of yeast Hsp70 cochaperones by intramolecular interactions involving their J-domains

Synergetic Support of Cartilage Homeostasis via Coupled Thermal-Hydrostatic Pressure Stimuli

S-acylation and lipid exchange at the ER-Golgi membrane contact sites regulate pathogen entry in human cells

Coordination of protein synthesis and degradation in mammalian cells

Why do we need so many proteins? A physical insight into the collaboration of Hsp70 and DnaJ

Bridging Native and Intrinsic Structures of Microhydrated Biomolecules by Cold Ion Spectroscopy

A molecular device for the redox quality control of GroEL/ES substrates

Recombinant Full-Length TDP-43 Oligomers Retain Their Ability to Bind RNAs, Are Not Toxic, and Do Not Seed TDP-43 Aggregation in Vitro

A fluorescent multi-domain protein reveals the unfolding mechanism of Hsp70

J-domain protein chaperone circuits in proteostasis and disease

Trans‐seeding of Alzheimer‐related tau protein by a yeast prion

Towards automating de novo protein design for novel functionalities: controlling protein folds and protein-protein interactions

Improved Cell-Free Transcription-Translation Reactions in Microfluidic Chemostats Augmented with Hydrogel Membranes for Continuous Small Molecule Dialysis

Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies

Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration

Repair or Degrade: the Thermodynamic Dilemma of Cellular Protein Quality-Control

Assessment of transferable forcefields for protein simulations attests improved description of disordered states and secondary structure propensities, and hints at multi-protein systems as the next challenge for optimization

Variants in USP48 encoding ubiquitin hydrolase are associated with autosomal dominant non-syndromic hereditary hearing loss