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The sirtuin family protein SIRT6 maintains pericentric heterochromatin silencing at human centromeres through deacetylation of a newly discovered substrate, H3K18, thus protecting cells against mitotic errors, genomic instability and cellular senescence.
An analysis of previously published data on fiber formation by sickle-cell hemoglobin reveals a universal curve when delay time is plotted against supersaturation (ratio of protein concentration to solubility).
RNA interference constrains antisense lncRNA transcriptomes, and its loss during budding yeast evolution is associated with an increase in genome-wide expression of antisense lncRNAs.
α-synuclein amyloid fibrils are associated with Parkinson's disease. SSNMR analyses now reveal the atomic structure of a pathogenic human α-synuclein fibril, providing a framework for understanding fibril nucleation, propagation and interactions with small molecules.
Structural and functional analyses of a new family of tick-derived C5 inhibitors in complex with inhibitor OmCI and therapeutic antibody eculizumab reveal diverse mechanisms for inhibition and provide insight into C5 activation by C5 convertases.
Ensemble kinetics and FRET analyses reveal the sequence of collective motions on the E. coli ribosome during translocation promoted by EF-G and allow identification of a new early forward swiveling of the SSU head.
The crystal structure of Drosophila melanogaster YL1 in complex with an H2A.Z–H2B dimer exposes a selective recognition mechanism distinct from those of other H2A.Z chaperones and suggests a hierarchical transfer mechanism mediating H2A.Z deposition.
Cancer-associated point mutations in the scaffold protein Axin derail Wnt signaling and promote tumor growth through formation of nonamyloid nanoaggregates that rewire the Axin interactome.
The crystal structure of human YL1, here established as an H2A.Z-deposition chaperone, in complex with an H2A.Z–H2B dimer reveals the molecular basis for the specificity of H2A.Z recognition.
New evidence that human telomerase RNA (hTR) degradation by EXOSC10 or DCP2 and XRN1 reduces telomerase activity when dyskerin is compromised suggests that RNA decay pathways may provide future therapeutic targets for telomere biology disorders.
Human orexin receptors (hOX1R and hOX2R) are GPCRs involved in sleep regulation. Structures of hOX1R bound to a selective antagonist or to a dual antagonist, functional assays and computational analyses reveal the basis for subtype selectivity.
USP7 deubiquitinase is now shown to prevent ubiquitination of SUMO chains of replisome proteins, thereby regulating DNA replication-fork progression and origin firing.
Structural and cellular analyses reveal that the presence of an isoform-specific α-helix in myosin VI determines whether this motor protein functions in endocytosis or cell migration.
During assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs), the RNA-binding protein (RBP) Gemin5 recognizes the snRNP code and interacts with the large Gemin2–SMN complex. So et al. now find that Gemin2 also interacts with U1-70K, thereby conferring a preferential advantage on U1 snRNP assembly, and they extrapolate that SMN–Gemin2 serves a general ribonucleoprotein-exchange function.
50 years ago, Jardetzky proposed the alternating-access model, which has shaped the theoretical understanding of how substrates are carried across cell membranes. Two studies now demonstrate that transporters from distinct families undergo unexpectedly large elevator-like movements and also suggest that an 'elevate and twist' mechanism is a common means of achieving alternating access across the membrane.
EaSeq, a user-friendly and freely available software tool, offers fast and comprehensive ChIP-sequencing data analyses, enabling experimentalists to easily extract information and generate hypotheses from genome-wide datasets.
NMR approaches are used to probe cotranslational folding of a nascent polypeptide with two domains in Escherichia coli. The work reveals that interactions with the ribosome inhibit acquisition of the native fold by the nascent chain.
Monitoring ribosomal translocation from five structural perspectives with pre–steady state smFRET defines intramolecular conformational events within the EF-G–GDP–bound ribosome as rate-determining steps of directional substrate translocation.