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Immunoglobulin M (IgM) is the most ancient antibody class and key mediator of the primary immune response. New structures reveal how it binds to its only class-specific receptor (FcμR) and offer a tantalizing clue to the role of FcμR in the IgM B cell receptor.
A study on a yeast model explores how ssDNA gaps induce cell death and genomic instability, implicating Rad9 and Rad51 in gap repair and protection. Gaps forming secondary structures trigger chromosome fragility, deletions, rearrangements, or cell death pathways, showing how gaps are a vulnerability in cancer cells with opportunity for selective targeting.
Two new structural studies of the GABA transporter subtype GAT1 reveal detailed snapshots of the GABA transport cycle, providing new mechanistic insights and blueprints for rational design of novel leads that target GABAergic systems.
Volume-regulated anion channels (VRACs) are critical for cell volume regulation, neuron–glia interaction, metabolism, and immunity. They are formed as heteromers of LRRC8 proteins with unknown stoichiometry. Two papers now reveal the structures of heteromeric LRRC8A and LRRC8C channels, providing insights into channel assembly and gating.
Gabapentinoids are first-line treatments for chronic pain but are associated with adverse side effects. A cryo-EM structure of gabapentin bound to its interaction site on the calcium channel α2δ subunit now paves the way for the rational design of analgesics with greater selectivity and a reduced potential for adverse effects.
The maturation of transfer RNAs requires the splicing of precursor tRNAs by specific endonucleases. New cryo-electron microscopy studies of the human splicing endonuclease bound to tRNAs shed light on how it cleaves and splices its substrates, explaining the function of eukaryote-specific enzyme subunits and rationalizing disease-associated mutations.
Cilia — or flagella, as they are interchangeably termed — are appendage-like organelles extending from eukaryotic cells. Several recent structural studies on intraflagellar transport (IFT) trains shed light on these fascinating complexes, including their assembly mechanism, stability, cargo recruitment and evolution.
The enzymatic activity of PARP1—which adds chains of (poly-ADP)-ribose (PAR) to proteins—initiates DNA repair by leading to more-accessible chromatin and recruitment of PAR-dependent DNA-repair proteins. New work shows that these PARP1-catalysed functions are redirected by the auxiliary factor HPF1 in cells.
White adipose tissue secretes the small polypeptide hormone leptin, which controls food intake and satiety. Unlike other metabolic hormones such as insulin and glucagon, leptin does not act on the major metabolic organs liver, muscle, and white adipose tissue, but instead exerts its primary function on the central nervous system.
A cardinal rule of DNA replication is to prevent any possibility of pre-replication complexes re-loading during S phase, risking genotoxic over-replication. But can this rule be broken in emergency situations to preserve genome integrity?
The RNA methyltransferase (MTase) METTL1 catalyzes N7-methylguanosine (m7G) modification at position 46 in human transfer RNAs (tRNAs). Its dysregulation drives tumorigenesis in many cancer types. Two papers now reveal the structural basis of this tRNA maturation event.
Recent studies offer new insight on the mechanisms of IP6-mediated HIV-1 capsid assembly. The immature Gag lattice enables enrichment of IP6 into virions, aiding capsid maturation. Structures of capsid protein (CA) assemblies reveal motifs serving as switches modulating the conformations of CA pentamers/hexamers and affect co-factor accessibility.
Sperm flagella of highly divergent eukaryotic species share an architectural plan. Despite their ostensible ultrastructural similarities, mammalian sperm flagella beat with an asymmetric waveform, in contrast to the symmetrical beats of other eukaryotic flagella. Structural findings elucidate the molecular basis for this evolutionary divergence.
AlphaFold2 has already changed structural biology, but its true power may lie in how it changes the way we think about cells and organisms. Two studies broadly assess its utility and limitations in providing structural models to shed light in areas such as mutations, protein–protein interactions, and phosphorylation.
