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Article
xTract: software for characterizing conformational changes of protein complexes by quantitative cross-linking mass spectrometry
Chemical cross-linking in combination with mass spectrometry generates distance restraints of amino acid pairs in close proximity on the surface of native proteins and protein complexes. In this study we used ...
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Article
Local slowdown of translation by nonoptimal codons promotes nascent-chain recognition by SRP in vivo
Analyses of yeast codon usage and ribosome profiling data reveal a nonoptimal codon cluster in the mRNAs of ER-targeted proteins, downstream of the SRP-binding site, that would slow down translation to promote...
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Article
Spatial sequestration of misfolded proteins by a dynamic chaperone pathway enhances cellular fitness during stress
The extensive links between proteotoxic stress, protein aggregation and pathologies ranging from ageing to neurodegeneration underscore the importance of understanding how cells manage protein misfolding. Usin...
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Article
Open AccessSuper-resolution fluorescence imaging of intracellular mutant huntingtin protein reveals a population of fibrillar aggregates co-existing with compact perinuclear inclusion bodies
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Article
The role of mutational robustness in RNA virus evolution
RNA viruses have extremely high mutation rates that are orders of magnitude greater than those of DNA-based organisms. Although some of these mutations are ben...
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Article
Evolutionary conservation of codon optimality reveals hidden signatures of cotranslational folding
Rare or nonoptimal codons that cause ribosomes to pause have been suggested to be important determinants of cotranslational folding. A revised translational efficiency scale, which considers tRNA abundance as ...
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Chapter
The interplay between the chaperonin TRiC and N-terminal region of Huntingtin mediates Huntington’s Disease aggregation and pathogenesis
Huntington’s Disease (HD) is a neurodegenerative disorder resulting from an expanded polyglutamine (polyQ) repeat in exon1 of the Huntingtin (Htt) protein. This polyQ expansion causes aggregation of the Htt pr...
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Article
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
Open AccessTracheostomy and mechanical ventilation weaning in children affected by respiratory virus according to a weaning protocol in a pediatric intensive care unit in Argentina: an observational restrospective trial
We describe difficult weaning after prolonged mechanical ventilation in three tracheostomized children affected by respiratory virus infection. Although the spontaneous breathing trials were successful, the pa...
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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
The chaperonin TRiC blocks a huntingtin sequence element that promotes the conformational switch to aggregation
The eukaryotic group II chaperonin TRiC can block polyQ tract aggregation, present in proteins such as Htt. Here the TRiC-Htt interaction is examined using in vitro and in vivo experiments, revealing that TRiC do...
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Article
The Hsp90 mosaic: a picture emerges
Hsp90s, molecular chaperones critically involved in many essential cellular processes, were the focus of a recent international conference held in Seeon, Germany. The scope of the conference ranged from struct...
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Article
Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies
The interactome of eukaryotic chaperonin TRiC/CCT is identified through a genome-wide approach, revealing an enrichment in large, multidomain proteins, or components of multimeric complexes, rich in hydrophobi...
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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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Article
Mechanism of lid closure in the eukaryotic chaperonin TRiC/CCT
Group II chaperonins, such as TriC/CCT, have a build-in lid that can cover the folding chamber and functions in an analogous way to the GroES-like proteins used by their Group I counterparts. Structural and mo...
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Article
Essential function of the built-in lid in the allosteric regulation of eukaryotic and archaeal chaperonins
Chaperonins are allosteric double-ring ATPases that mediate cellular protein folding. ATP binding and hydrolysis control opening and closing of the central chaperonin chamber, which transiently provides a prot...
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Article
The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions
Misfolding and aggregation of proteins containing expanded polyglutamine repeats underlie Huntington's disease and other neurodegenerative disorders1. Here, we show that the hetero-oligomeric chaperonin TRiC (als...
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Article
Protein quality control: chaperones culling corrupt conformations
Achieving the correct balance between folding and degradation of misfolded proteins is critical for cell viability. The importance of defining the mechanisms and factors that mediate cytoplasmic quality contro...
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Protocol
Aberrant Protein Folding as the Molecular Basis of Cancer
Under normal growth conditions, tumor-suppressor proteins and oncogenes play key roles in the tight regulation of cell division (1). Tumorigenesis often arises from mutations that interfere with the appropriate f...
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Article
Where chaperones and nascent polypeptides meet
Two recent studies provide evidence for a direct interaction between the ribosomal protein L23 at the exit tunnel of the ribosome and the bacterial chaperone trigger factor, and between the eukaryotic L23 homo...
