|Nature Structural aamp; Molecular Biology - Issue - nature.com science feeds|
Recognition of nucleic acids is a key strategy of the innate immune system to detect infectious organisms and tissue damage. Toll-like receptor (TLR) 8 was long assumed to be a receptor for single-stranded (ss) RNA. Unexpected findings now suggest that TLR8 recognizes RNA degradation products rather than ssRNA and that synergistic binding of two uridine-containing agonists at distinct sites of the receptor leads to activation of the innate immune response.
Little is currently known about the molecular determinants of energy barriers along enzyme catalytic pathways. Kern and co-workers have studied this question in adenylate kinase (Adk) and now reveal that a single Mg2+ ion can accelerate two distinct steps, thus uncovering an unexpected dual role for this ubiquitous cofactor.
The structural rules governing the curving folds of solenoid proteins, as distilled down to the level of the underlying sequence repeats, provide designers with the tools to reliably fashion new variants with tunable geometries. Bespoke leucine-rich repeat (LRR) scaffolds, as recognition proteins, can now be tailored to better fit their targets.
The ryanodine receptor (RyR), an ion channel regulating intracellular calcium release in excitable cells, has been challenging for structural analysis because of its colossal proportions compared to most other ion channels. Three independent groups have now used recent technological advancements in single-particle cryo-EM to make giant strides in solving the structure of this elusive protein complex.
Toll-like receptors (TLRs) have key roles in innate immunity. Here, Shimizu and colleagues report crystal structures of TLR8 in complex with single-stranded RNA that reveal the molecular basis for recognition of a natural ligand.
Oxidative stress induces a number of cellular responses. Silva et al. uncover a peroxide-mediated K63-linked polyubiquitination pathway, and identify its targets and regulators.
Structural, computation and kinetics approaches reveal the energy landscape of catalysis by adenylate kinase and show that the cofactor Mg2+ activates two distinct molecular events in the reaction cycle: phosphoryl transfer and lid opening.
Theγ-tubulin ring complex (γTuRC) nucleates microtubules in the cell. The functional, closed state of yeast γTuRC is now visualized, and its microtubule-nucleating activity is found to be species specific.
Aquarius is an RNA helicase associated with spliceosomes. Lührmann, Pena and colleagues now provide structural insights into how Aquarius is recruited to the spliceosome, revealing a new spliceosomal building block that aids in Aquarius positioning.
Proteins with charged amino acid residues encounter an electric force as they transit through membranes holding membrane potential. Von Heijne and colleagues measure this force to assess how membrane electrostatics contributes to translocation dynamics.
CtIP helps maintain genomic stability by promoting DNA double-strand-break repair. Structural and biophysical analyses now show that the N terminus of human CtIP forms a tetrameric structure that is required for resection of broken DNA ends to permit their repair by homologous recombination.
Structural, biophysical and genetic analyses reveal that Schizosaccharomyces pombe Ctp1 forms a flexible tetramer with multivalent DNA-binding and bridging activities that contribute to Ctp1's role in repair of DNA double-strand breaks.
Leucine-rich repeats (LRRs) can form horseshoe-like structures with different curvatures in nature. A computational approach now allows the design of 12 new LRR proteins with precise curvatures, using defined building blocks and junction modules.
|Nature Structural aamp; Molecular Biology - AOP - nature.com science feeds|
Aβ peptide aggregation is associated with Alzheimer's disease, and Aβ fibrils can catalyze formation of toxic oligomers. Molecular chaperone Brichos binds to the fibril surface, inhibiting the catalytic cycle in vitro, and limits Aβ toxicity.
Crystal structures of the bacterial vitamin C transporter UlaA, a member of the AG family of the phosphoenolpyruvate-dependent phosphotransferase system, provide insights on binding to ascorbate and its transport across the cell membrane.
Tumor-suppressor protein CYLD cleaves linear and Lys63-linked ubiquitin chains. Structures of CYLD USP domain with Met1- and Lys63-linked diubiquitins and biochemical analyses reveal the mechanism for dual specificity and provide insight into tumor-associated mutations.
Genome-wide DNA polymerase usage maps determined in fission yeast, using a new sequencing strategy based on ribonucleotide misincorporation, track the division of labor between replicative polymerases and reveal locations and efficiencies of replication origins.
The crystal structure of Yersinia enterocolitica kinase YopO in complex with monomeric actin, together with biochemical analyses, reveals that YopO uses actin as bait to disrupt host cytoskeleton function and prevent phagocytosis.
The identification of a new subclass of circular RNAs that are predominantly nuclear and promote transcription of their parental genes reveals a new regulatory function for these noncoding RNAs.
The proteasome initiates protein degradation at disordered regions within substrates. The proteasomal sequence preferences for the amino acid composition of these regions identified here affect protein half-life and explain unusual stability trends.
Human DNA Polθ can mediate microhomology-mediated end-joining (MMEJ) of DNA molecules in cells and in vitro. Biochemistry work shows that Polθ promotes formation of DNA synapses and strand annealing, activities that require insertion loop 2.
The neuronal sorting receptor SorLA protects against Alzheimer's disease by binding Aβ peptides. Three new structures of the Vps10p Aβ-binding domain in ligand-free and ligand-bound forms explain the basis of SorLA peptide recognition.
New biochemical analyses in Xenopus cell-free extracts show that two replication forks must converge on a DNA interstrand cross-link (ICL) to permit translesion synthesis and repair.
HydEn-seq, a new sequencing method that maps the distribution of ribonucleotides misincorporated by low-fidelity DNA polymerases in budding yeast, reveals unexpected strand-specific replication patterns in both nuclear and mitochondrial genomes.
Serial femtosecond crystallography of the humanδ-opioid receptor in complex with an endomorphin-derived peptide reveals interactions that are important for understanding the pharmacology of opioid peptides and developing analgesics with reduced side effects.
A high-resolution cryo-EM structure of yeast eIF3-bound 40S ribosomal subunits reveals the network of interactions between eIF3 subunits.