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Cryo-EM structures of the transcription preinitiation complex in the presence of the +1 nucleosome show how the general transcription factor TFIIH can interact with the nucleosome at several positions.
Cryo-EM has facilitated structural studies of membrane proteins, but inactive GPCRs have remained inaccessible due to their small size. Robertson et al. demonstrate a common nanobody-based approach to streamline the determination of such structures.
Luan et al. find that CTCF shapes the transcriptional landscape in part by suppressing the initiation of upstream antisense transcription at hundreds of divergent gene promoters.
Schmidpeter and colleagues showed that anionic lipids bind to pacemaker ion channels and increase their activity by acting like keys that unlock salt bridges at the channel gates.
Here, the structure of poly(UG) RNA reveals an unusual left-handed quadruplex, or ‘pUG fold’. The pUG fold marks RNAs as vectors for gene silencing in C. elegans by recruiting RNA-dependent RNA polymerase for siRNA synthesis.
Here, the authors evaluate the performance of AlphaFold2 and its predicted structures on common structural biological applications, including missense variants, function and ligand binding site prediction, modeling of interactions and modeling of experimental structural data.
Morey and colleagues identify a dual function of CoREST in regulating sensitivity and resistance to endocrine therapies in breast cancer. This work also provides a pre-clinical model for study of the conversion of luminal/ER+ to basal/ER− breast cancer.
Cryo-EM structures of simian immunodeficiency virus (SIV) envelope trimers with neutralizing antibodies reveal mechanisms—conserved throughout SIV evolution—of immune evasion through extended variable loops and glycan shielding, involving both N- and O-linked glycans.
The selection of polyadenylation signals defines 3′UTR length. The authors find that MYC alters the expression of factors that repress strong polyadenylation signals at the distal end of genes, boosting usage of suboptimal, proximal polyadenylation signals and promoting the translation of cell cycle-related genes.
Cryo-EM structures of the AAA+ ClpAP•ClpS protease-adaptor complex show degron-like ClpS binding, coordinated by pore-1 loops from either the D1 or the D1 and D2 rings of ClpA. D1-pore-2-loop activity is critical for ClpS-assisted degradation.
The authors used massively parallel splicing assays and statistical learning to decode and predict the erroneous splicing choices made by disease-relevant mutant sequences, which annotates intronic variants potentially for clinical usage.
This study identifies protein structural changes in cerebrospinal fluid of people with Parkinson’s disease relative to healthy individuals and proposes the concept of structural disease biomarkers. It also analyzes proteome structural variability in healthy people.
The tumor suppressor ARF is retained by nucleophosmin (NPM) in nucleoli, but shifted out upon DNA damage. In this study, the authors show that cytochrome c triggers a conformational change on NPM, driving ARF release and controlling protein trafficking.
Here, Dimitrova et al. examine how CKM–Mediator and Polycomb shape 3D chromosome interactions in ESCs and discover that gene activation during differentiation is independent of pre-formed interactions but depends on recruitment of the core Mediator.
The authors present Modeling immuno-OligoSTORM (MiOS), a super-resolution imaging and computational strategy to model 3D gene folding at multiple genomic scales, reaching nucleosome resolution at the single-gene level.
Happ et al. uncover an unusual regulatory mechanism in the Hedgehog signaling pathway, which enables a G protein-coupled receptor to physically block the enzymatic activity of a major cellular kinase.
The high-resolution crystal structure of the SHOC2–MRAS–PP1C complex provides insights into the complex assembly, RAF dephosphorylation, MRAS selectivity versus canonical RAS isoforms, and the impact of Noonan syndrome mutations on complex formation.
Escherichia coli SSB enriches Pol IV polymerase at lesion-stalled replication forks, promoting translesion synthesis. Loss of this enrichment increases repriming of DNA synthesis, revealing a pivotal role of SSB in the pathway choice of stalled replication forks.
The Braun lab shows that the conserved nuclear membrane protein Lem2 interacts with the MTREC complex of the nuclear-exosome pathway to promote recruitment and degradation of ncRNAs and meiotic transcripts at the nuclear periphery in Schizosaccharomycespombe.
A cryo-EM structure of disease-related human Y145Stop prion protein amyloid fibrils explains species-dependent seeding barriers in prion protein amyloid propagation.