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The ATM kinase is shown to be recruited to sites of DNA damage, where it phosphorylates H2AX and triggers the G2-M checkpoint, in the absence of both MRN and Ku70–Ku80.
Mig6 phosphorylation at two consecutive tyrosines induces rearrangements that lead to Mig6 sticking to and inhibiting the same EGFR that catalyzed its phosphorylation. This mechanism may serve as a basis for inhibition of oncogenic EGFR variants.
The cocrystal structure of bacterial alarmone ZMP with its cognate riboswitch reveals how the two subdomains of the latter mediate ligand recognition. Supporting biochemical analyses show that ligand binding affinity and transcription antitermination are modulated by the interdomain linker length.
Extensive mutant cycle analysis provides a map of the residues that contribute to stability and activation-associated conformational dynamics of the Gαi1 protein in nucleotide-bound states and in complex with the G protein–coupled receptor rhodopsin.
PsbS is a transmembrane photosystem II protein essential for photoprotection in plants. Crystal structures show that PsbS is not a canonical pigment-binding protein and provide insights into its pH-dependent activation mechanism.
Dual effector binding to the small GTPase Rab11 suggests that membrane-targeting complexes involved in vesicular transport might assemble through multiple weak interactions to create high-avidity assemblies.
Biochemical and structural analyses show that Rubisco accumulation factor 1 (Raf1) stabilizes RbcL dimers, which then assemble into octamers. Raf1 is then displaced by RbcS, thus yielding the Rubisco holoenzyme.
The Mycobacterium tuberculosis necrotizing toxin (TNT) is shown to cause toxicity by hydrolyzing NAD+ in the host cell. The crystal structure of TNT bound to its immunity factor reveals a new NAD+ glycohydrolase fold.
New data show that depletion of histone chaperone CAF-1 in mouse embryonic stem (ES) cells induces early embryonic-like cells that exhibit gene-expression patterns and reprogramming efficiencies characteristic of 2-cell-stage populations that arise spontaneously in ES-cell culture, thus suggesting that altered chromatin assembly contributes to differences in stem-cell plasticity.
O-GlcNAcylation is a post-translational modification catalyzed by O-GlcNAc transferase. Here, a high-throughput activity assay combined with mass spectrometric and crystallographic analyses sheds light on the substrate recognition and specificity of O-GlcNAc transferase.
Plasmepsin V is an aspartyl protease essential for export of effector proteins to Plasmodium-infected erythrocytes. A new inhibitor blocks plasmepsin V and inhibits parasite growth; it has also allowed solving the structure of P. vivax plasmepsin V.
Structural studies of human polysialyltransferase ST8SialII in apo form and in complex with donor sugar and sulfated glycan acceptor shed light on the substrate binding and specificity as well as the catalytic activity of this class of polysialyltransferases.
Flexible filamentous plant viruses, which cause substantial crop damage worldwide, have eluded structural characterization so far. The cryo-EM structure of BaMV now reveals the virus architecture and the structural basis of its flexibility.
Chromatin reassembly after replication requires recycling of old and deposition of new histones. Structural insights into how MCM2, part of the replicative helicase, interacts with H3–H4 suggest a function in histone recycling at replication forks.
Chemical genetics, proteomics and biochemistry are used to probe the functions of SR protein kinases. An identified target of Dsk1 is spliceosomal protein Bpb1 (SF1), whose phosphorylation increased its binding to introns with nonconsensus splice sites.
NMR relaxation dispersion measurements reveal the conformational dynamics of the mitochondrial ADP/ATP carrier and show that the ADP substrate facilitates interconversion between the predominant cytosol-facing state and a sparsely populated excited state.
Extensive glycan microarray and structural analyses reveal that human intelectin-1 interacts selectively with microbial glycan epitopes through recognition of a terminal 1,2-diol group, an interaction that would be blocked in human glycans such as α-Neu5Ac.
Structural analyses capture RING E3 ligase RNF4 bound to Ube2V2–Ubc13 E2 complex charged with ubiquitin and, along with functional assays, reveal the basis for synthesis of K63-linked chains.
The crystal structure of human stearoyl-CoA desaturase-1 in complex with its natural substrate provides a close-up view of a key enzymatic step in the synthesis of unsaturated fatty acids.
The structure of the ligand-free HIV-1–Env trimer allows conformational fixation of Env and generation of an antigen that binds CD4 with high affinity and is recognized by broadly neutralizing antibodies but not poorly neutralizing ones.