Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Iboxamycin (IBX) is a new oxepanoprolinamide antibiotic based on clindamycin. Crystal structures of IBX in complex with bacterial ribosomes uncover the structural mechanism of its activity against multidrug-resistant pathogens and reveal key interactions with tRNAs and 23S rRNA, including resistance-conferring rRNA methylations.
New work from Guberovic et al. sheds light on the evolution of the histone variant macroH2A1.1 and its relationship with the NAD+-using poly(ADP-ribose) polymerase PARP1. Their study shows that macroH2A1.1 has been a nuclear regulator of NAD+ flux as far back evolutionarily as pre-metazoan protists, but has been loosening the reins on PARP1, thus expanding PARP1’s cellular roles.
Transcription of eukaryotic protein-coding genes involves co-activator complexes, including TFIID and SAGA. A new study has determined the first high-resolution cryo-EM structure of the human SAGA complex, and has implications for defining SAGA function during multiple stages of eukaryotic transcription.
Structural studies of a positive allosteric modulator of the adenosine A1 receptor demonstrate the mechanisms by which stabilization of the GPCR–G protein complex bound to its endogenous agonist yields analgesic efficacy in an animal model of neuropathic pain.
The critical event in KRAS signaling and oncogenic transformation is activation of the RAF–MEK–MAPK cascade. This requires assembly of a multiprotein–lipid complex on the plasma membrane. In a tour de force of modeling, Mysore et al. now provide the first glimpse of what this structure may actually look like.
CTCF is a conserved DNA- and RNA-binding protein with roles in genome folding and transcriptional regulation. Two recent studies investigated how CTCF knockout perturbs genome biology and derails embryogenesis in zebrafish and Drosophila melanogaster, revealing contrasting effects across species.
Emerging findings provide compelling evidence that the BRCA1-binding partner BARD1 contributes yet further to BRCA1 function. BARD1 is crucial for positioning the E2 ubiquitin-conjugating enzyme that confers specificity of its ligase to residues on histone H2A, and BARD1 also promotes DNA damage–induced chromatin recruitment through an interaction with ubiquitin-conjugated Lys13 or Lys15 of H2A on the nucleosome core particle.
Molnupiravir, a wide-spectrum antiviral that is currently in phase 2/3 clinical trials for the treatment of COVID-19, is proposed to inhibit viral replication by a mechanism known as ‘lethal mutagenesis’. Two recently published studies reveal the biochemical and structural bases of how molnupiravir disrupts the fidelity of SARS-CoV-2 genome replication and prevents viral propagation by fostering error accumulation in a process referred to as ‘error catastrophe’.
The folding of ribosomal RNAs is central to the biogenesis of the mitoribosome and is a complex, stepwise process. Five recent cryo-EM studies detail the late steps of the folding and maturation of the human mitoribosomal large subunit RNA that forms the catalytic core of the ribosome: the peptidyl transferase center (PTC).
Dimeric multidomain metabotropic glutamate receptors modulate excitatory neurotransmission in the brain. Three articles in Nature provide unparalleled insights into how glutamate and drug-like molecules induce asymmetric shape changes in these multidomain receptors to promote coupling to an intracellular protein partner.
Atomic force microscopy (AFM) is unique in visualizing functional biomolecules in aqueous solution at ~1 nm resolution. By borrowing localization methods from fluorescence microscopy, AFM has been shown to discern structural domains that may be separated by only a few Ångströms.
A new cryo-EM study reveals how ATP hydrolysis in the p97 ATPase is coordinated to unfold the protein’s substrates and provides new foundations for the design of small molecule therapeutics targeting p97 in cancer, neurodegeneration and viral infection.
The autophagy protein Atg8 regulates autophagosome biogenesis and mediates cargo recruitment in different types of selective autophagy, but the molecular mechanisms mediating Atg8 functions during autophagosome biogenesis have been unclear. A study published in Nature Structural & Molecular Biology now shows that lipidated Atg8 possesses physicochemical activity that regulates membrane morphology, which underlies efficient autophagosome biogenesis.
