18 Result(s)
within
Judith Frydman
Science, Humanities and Social Sciences, multidisciplinary
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Article
Open AccessA structural vista of phosducin-like PhLP2A-chaperonin TRiC cooperation during the ATP-driven folding cycle
Proper cellular proteostasis, essential for viability, requires a network of chaperones and cochaperones. ATP-dependent chaperonin TRiC/CCT partners with cochaperones prefoldin (PFD) and phosducin-like protein...
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Article
Open AccessA lethal mitonuclear incompatibility in complex I of natural hybrids
The evolution of reproductive barriers is the first step in the formation of new species and can help us understand the diversification of life on Earth. These reproductive barriers often take the form of hybr...
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Open AccessCryoET reveals organelle phenotypes in huntington disease patient iPSC-derived and mouse primary neurons
Huntington’s disease (HD) is caused by an expanded CAG repeat in the huntingtin gene, yielding a Huntingtin protein with an expanded polyglutamine tract. While experiments with patient-derived induced pluripot...
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Article
Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis
Ageing is accompanied by a decline in cellular proteostasis, which underlies many age-related protein misfolding diseases1,2. Yet, how ageing impairs proteostasis remains unclear. As nascent polypeptides represen...
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Author Correction: Cotranslational prolyl hydroxylation is essential for flavivirus biogenesis
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Open AccessCryoEM reveals the stochastic nature of individual ATP binding events in a group II chaperonin
Chaperonins are homo- or hetero-oligomeric complexes that use ATP binding and hydrolysis to facilitate protein folding. ATP hydrolysis exhibits both positive and negative cooperativity. The mechanism by which ...
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Article
Cotranslational prolyl hydroxylation is essential for flavivirus biogenesis
Viral pathogens are an ongoing threat to public health worldwide. Analysing their dependence on host biosynthetic pathways could lead to effective antiviral therapies1. Here we integrate proteomic analyses of pol...
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Open AccessNative mass spectrometry analyses of chaperonin complex TRiC/CCT reveal subunit N-terminal processing and re-association patterns
The eukaryotic chaperonin TRiC/CCT is a large ATP-dependent complex essential for cellular protein folding. Its subunit arrangement into two stacked eight-membered hetero-oligomeric rings is conserved from yea...
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Open AccessDisease-related Huntingtin seeding activities in cerebrospinal fluids of Huntington’s disease patients
In Huntington’s disease (HD), the mutant Huntingtin (mHTT) is postulated to mediate template-based aggregation that can propagate across cells. It has been difficult to quantitatively detect such pathological ...
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Article
Open AccessREP-X: An Evolution-guided Strategy for the Rational Design of Cysteine-less Protein Variants
Site-specific labeling of proteins is often a prerequisite for biophysical and biochemical characterization. Chemical modification of a unique cysteine residue is among the most facile methods for site-specifi...
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Article
Distinct proteostasis circuits cooperate in nuclear and cytoplasmic protein quality control
Protein misfolding is linked to a wide array of human disorders, including Alzheimer’s disease, Parkinson’s disease and type II diabetes1,2. Protective cellular protein quality control (PQC) mechanisms have evolv...
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Open AccessHsp90 shapes protein and RNA evolution to balance trade-offs between protein stability and aggregation
Acquisition of mutations is central to evolution; however, the detrimental effects of most mutations on protein folding and stability limit protein evolvability. Molecular chaperones, which suppress aggregatio...
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Article
Open AccessMultivalent contacts of the Hsp70 Ssb contribute to its architecture on ribosomes and nascent chain interaction
Hsp70 chaperones assist de novo folding of newly synthesized proteins in all cells. In yeast, the specialized Hsp70 Ssb directly binds to ribosomes. The structural basis and functional mode of recruitment of Ssb ...
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Article
Cotranslational signal-independent SRP preloading during membrane targeting
The signal recognition particle (SRP) preferentially binds peptides destined for secretion before peptide-targeting signals are translated through recognition of elements in their mRNA, including non-coding se...
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Open AccessCellular Inclusion Bodies of Mutant Huntingtin Exon 1 Obscure Small Fibrillar Aggregate Species
The identities of toxic aggregate species in Huntington's disease pathogenesis remain ambiguous. While polyQ-expanded huntingtin (Htt) is known to accumulate in compact inclusion bodies inside neurons, this is...
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Article
Mechanism of folding chamber closure in a group II chaperonin
Chaperonins are large, cylindrical complexes that assist in the folding of cellular proteins in an ATP-dependent manner. Group II chaperonins are present in eukaryotes and archaea and consist of two back-to-ba...
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Article
Misfolded proteins partition between two distinct quality control compartments
The accumulation of misfolded proteins in intracellular amyloid inclusions, typical of many neurodegenerative disorders including Huntington’s and prion disease, is thought to occur after failure of the cellul...
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Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones
The folding of polypeptides emerging from ribosomes was analysed in a mammalian translation system using firefly luciferase as a model protein. The growing polypeptide interacts with a specific set of molecula...
