|Nature Structural aamp; Molecular Biology - Issue - nature.com science feeds|
The Eighth International Conference on the Hsp90 Chaperone Machine took place in November 2016 at the Seeon Abbey in Germany. This year's program focused on a variety of topics, reflecting Hsp90's diverse roles in cellular and physiological function. The highlights included structural insights into the Hsp90 folding mechanism and conformational dynamics, post-translational modifications, client protein maturation, Hsp90 cochaperone function and Hsp90's role in disease physiology.
Warfarin has been the most widely prescribed anticoagulant for decades. It functions by inhibiting the membrane enzyme vitamin K epoxide reductase (VKOR), but the molecular details of this effect have remained elusive. Two new studies shed light on the warfarin-VKOR interaction. The work has implications for precision medicine and could guide drug discovery.
Little is known about the functions of long noncoding RNAs compared with the amount of accumulated knowledge concerning protein-mediated mechanisms. A report now proposes a novel RNA classification based on similar kinetics of RNA synthesis, processing and turnover, and the authors predict that RNAs within each class might share functional properties.
The site of HIV genome integration is likely a contributing factor in viral gene expression, but such context-specific effects are difficult to demonstrate at the population level. A new approach overcomes this obstacle by tracking individual, barcoded viruses to investigate the relationship between integration site location and the corresponding viral transcription, thereby providing insights essential for understanding HIV production, latency and reactivation.
Determining the molecular mechanisms responsible for trinucleotide DNA repeat expansions is critical, as such expansions underlie many neuromuscular and neurodegenerative disorders. Mirkin and colleagues now propose that large-scale expansions of trinucleotide repeats can be generated by DNA-break-induced replication.
Loss of function of the CFTR anion channel leads to cystic fibrosis, the most common inherited condition in humans of European origin. A recently reported structure for CFTR at 3.7-Å resolution reveals an unexpected 'lasso' domain and provides new insights into channel function in healthy individuals and in people with cystic fibrosis.
Genetic and biochemical assays reveal that carbon monoxide produced by heme catabolism influences circadian rhythm in mammals by altering the activity of transcription factor CLOCK–BMAL1 at clock-gene targets.
The enzyme FICD was previously known to AMPylate the ER-resident chaperone BiP, inactivating the chaperone. Mammalian FICD is now shown to catalyze the removal of the AMP group from BiP.
New data reveal that telomere length is maintained in human pluripotent stem cells through the opposing activities of telomerase-meditated elongation and telomere trimming mechanisms promoted by HR factors.
Cryo-EM analysis captures three states of the human Rad51 recombinase and visualizes structures of presynaptic and postsynaptic filaments as well as a synaptic complex in the process of DNA-strand exchange.
Barcoded HIV ensembles (B-HIVE) provides a new approach to map HIV integration sites and to determine how genomic context influences proviral transcription activity and response to latency-reversing agents.
A newly developed assay in yeast reveals that large-scale expansions of trinucleotide repeats can occur in a single step, rather than through several small-scale events.
Large-scale sequencing approaches reveal that the genetic code of Euplotes ciliates supports widespread ribosomal frameshifting at stop codons, and that additional mechanisms are required for efficient translation termination.
Mass spectrometry and biochemical analyses reveal that the major form of VKOR found in cells features a disulfide bond between Cys51 and Cys132, and this intermediate is the target of the anticoagulant drug warfarin.
The binding sites for the anticoagulant drug warfarin and for vitamin K on the human VKOR are determined through biochemistry and computational approaches. The results indicate a competitive mechanism of inhibition of VKOR by warfarin.
Quantitative assessment of transcription, splicing, degradation, localization and translation of coding and noncoding genes allows classification of RNAs on the basis of their metabolism and may aid in inference of lncRNA function.
|Nature Structural aamp; Molecular Biology - AOP - nature.com science feeds|
Crystal structures of a localization element of ASH1 mRNA alone, in complex with its nuclear shuttling protein She2p, and in the cytoplasmic complex with She2p and She3p reveal a step-wise maturation pathway.
Cryo-EM structures of full-length human PC2 reveal two distinct channel states: an open conformation and a blocked conformation with Ca2+ bound at the entrance of the selectivity filter.
Cryo-EM and NMR analyses of the E. coli replisome show how DNA-end fraying after mismatch incorporation at the polymerase active site enables substrate ends to reach the‘proofreading’ exonuclease site for mismatch removal.
A combination of SILAC-MS, genome-wide nucleosome mapping and live-cell imaging reveal rapid histone degradation and global chromatin decompaction after the induction of DNA double-strand breaks in S. cerevisiae.
The cryo-EM structure of immature Zika virus shows partially ordered capsid proteins and reveals differences between pre-epidemic and epidemic strains at protein interfaces within the trimeric spikes.
The yeast ribosome-associated complex (RAC) is formed by Hsp40 protein Zuo1 and the atypical Hsp70 chaperone Ssz1. Structural analyses show Ssz1 in a hybrid conformation between the open and closed state and its substrate-binding domain completed by Zuo1.
Cryo-EM structures of secretin GspD in type II secretion systems from Escherichia coli and Vibrio cholera reveal a pentadecameric architecture, with three rings in the periplasm andβ-strand-enriched gates on the outer membrane.
HDL particles transport cholesterol and contain apolipoprotein A-I as their major protein. The solution structure of discoidal HDL particles reconstituted with a shortened apoA-I is now solved via a combination of NMR and EPR analyses.
The crystal structure of MurJ, a bacterial lipid II flippase involved in peptidoglycan biosynthesis and a member of the MOP transporter superfamily, reveals an inward-facing conformation and points to an alternating-access mechanism.
The cryo-EM structure of human polycystin-2 (PC2) in a closed conformation reveals a domain located above the pore filter, forming an upper vestibule and making contacts with the pore and voltage-sensor-like domains.
The structure of GlyRα3 in complex with a selective potentiator that decreases neuropathic pain in an animal model identifies a novel allosteric regulatory mechanism.
Genome-wide analyses of S. cerevisiae replisome mobility reveal overlapping roles of Pif1 and Rrm3 helicases in alleviating replication-fork arrest at tRNA genes.
Crystal structures of human APOBEC3A and a chimera of APOBEC3B and APOBEC3A bound to ssDNA reveal an unanticipated‘U-shaped’ binding mode and provide insight into target selectivity.