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The symbiotic gut bacterium Bacteroides fragilis produces unique α-galactosylceramides from host dietary branched-chain amino acids, which are presented as CD1d ligands and immunomodulate natural killer T cells.
Cryo-electron microscopy studies show that dynamic coordination of Na+ in the ion channel of Dispatched homologue 1 and the transmembrane Na+ gradient have key roles in exporting lipid-modified Hedgehog protein signal.
Cryo-EM structure of Nf1 protein is reported, revealing closed and open conformations that regulate interaction with Ras oncogene, setting the stage for understanding the mechanistic action of Nf1 and how disease mutations lead to dysfunction.
The cryo-electron microscopy structure of domain 1 of the LDLRAD3 receptor in complex with virus-like particles of Venezuelan equine encephalitis virus (VEEV) provides insights into the assembly and entry of VEEV and other alphaviruses.
Structural studies of the complex of anaplastic lymphoma kinase and leukocyte tyrosine kinase and their activating cytokines identify unique architectural features of the complex, and provide a novel mechanistic paradigm among receptor tyrosine kinases.
Structure of human nuclear pore complex in its cellular environment reveals a substantially dilated central channel and shows that its nucleoplasmic and cytoplasmic rings restrict channel dimensions and create membrane asymmetry at the inner ring.
Structures of the Cas4–Cas1–Cas2 complex from Geobacter sulfurreducens show that a 3′-overhang in the protospacer adjacent motif is required for complex assembly and spacer insertion into the CRISPR array.
Cryo-electron microscopy structures of tau filaments from progressive supranuclear palsy and other tauopathies reveal new filament conformations, and suggest that tauopathies can be classified on several different levels according to their filament folds.
Cryo-electron microscopy structures of the voltage-gated potassium channel Kv4.2 alone and in complex with auxiliary subunits (DPP6S and/or KChIP1) reveal the distinct mechanisms of these two different subunits in modulating channel activity.
Cryo-electron microscopy structures of the luteinizing hormone–choriogonadotropin receptor (LHCGR), in complex with Gs and in various states of activation, reveal a distinct mechanism of receptor activation, with implications for drug discovery.
The authors report the structures of glutamate-gated kainate receptors in complex with NETO2 in both the resting and the desensitized states and reveal how kainate receptors in the brain are regulated by NETO2.
Crystal structures of the hepatitis C virus (HCV) glycoprotein E2 in complex with CD81 reveal the conformational changes that occur in E2 after binding of CD81 and the effects of pH on binding affinity.
MIPS521, a positive allosteric modulator of the adenosine A1 receptor, has analgesic properties in a rat model of neuropathic pain through a mechanism by which MIPS521 stabilizes the complex between adenosine, receptor and G protein.
Structural, functional and localization studies reveal that Geobacter sulfurreducens pili cannot behave as microbial nanowires, instead functioning in a similar way to secretion pseudopili to export cytochrome nanowires that are essential for extracellular electron transfer.
Structural and mechanistic data of the ADP-ribosyltransferase DarT demonstrate the role of ADP-ribosylation of DNA by this enzyme in generating toxicity and regulating cellular signalling processes in bacteria.
The cryo-electron microscopy structure of a newly identified, early spliceosomal complex reveals the mechanism by which the RNA helicase Prp5 enhances the fidelity of the excision of introns from precursor mRNAs.
The authors elucidate the mechanisms for the ubiquitylation specificity and recruitment of the ubiquitin ligase complex BRCA1–BARD1 to damaged DNA within chromatin to facilitate homologous recombination.
AlphaFold is used to predict the structures of almost all of the proteins in the human proteome—the availability of high-confidence predicted structures could enable new avenues of investigation from a structural perspective.
The human monoclonal antibody S2X259 cross-reacts with spike proteins from all clades of sarbecovirus, and provides prophylactic and therapeutic protection in vivo against parental SARS-CoV-2 and emerging variants of concern.
Cryo-electron microscopy structures of human Cav2.2 in the presence or absence of ziconotide reveal the molecular basis of the specificity of this painkiller for Cav2.2, and provide insights into electromechanical coupling in Cav channels.
Cryo-EM structures of human calcium-sensing receptor reveal intrinsic asymmetry in the receptor homodimer upon activation that is stabilized by calcimimetic drugs adopting distinct poses in the two protomers, priming one protomer for G-protein coupling.
Cryo-electron microscopy structures of homo- and heterodimers of mGlu2 and mGlu7 provide insights into their dimerization modes and the subunit conformational changes that characterize the activation of these class C G-protein-coupled receptors.
Cryo-electron microscopy structures of PCFT in a substrate-free state and bound to the antifolate drug pemetrexed provide insights into how this protein recognizes folates and mediates their transport into cells.
A cryo-electron microscopy structure of the inner membrane complex of the ESX-5 type VII secretion system of Mycobacterium tuberculosis reveals an important role of interactions with MycP5 protease for complex integrity.