Articles in 2017

The structure of C3b in complex with factor I and a shortened version of factor H, along with functional analyses, leads to a mechanistic model for how regulators determine sequential cleavage events on C3b.

Asparagine endopeptidase (AEP) cleaves human α-synuclein at Asn103, yielding a fragment with higher aggregation propensity than that of the full-length protein. Truncated α-synuclein is also more neurotoxic and leads to dopaminergic neuronal loss and motor impairments in mice.

Long noncoding (lnc)RNAs are postulated to control diverse biological processes by modulating transcription, yet for most lncRNAs evidence supporting this function has been lacking. A new report describes the role of a novel class of lncRNAs—chromatin-associated enhancer RNAs or cheRNAs—in the regulation of proximal gene expression.

Nature research journals announce new reporting summaries to promote transparency, and our editors welcome early-career researchers to the Springer Nature office in New York to discuss careers in scientific publishing.

The envelope glycoprotein spike, the sole antigen on the Lassa virus (LASV) surface, constitutes the focal point of the host neutralizing immune response. A high-resolution structure of the trimeric LASV glycoprotein in an antibody-bound form illuminates the molecular architecture of the antigen and reveals the mode of action of the most abundant known class of Lassa-specific human neutralizing antibodies.

Cytoplasmic dyneins transport cellular components from the periphery toward the center of the cell. By moving cargoes along microtubules, dyneins ensure proper cell division, regulate exchange of materials between organelles, and contribute to the internal organization of eukaryotic cells. Two recent studies show that, upon dimerization, cytoplasmic dyneins intrinsically adopt an autoinhibited configuration that can be relieved by other factors to precisely control motor activity and regulate dynein-based transport.

Functional characterization of chromatin enriched lncRNAs (cheRNAs) reveals their role as cis-acting transcriptional activators that couple enhancers at sites of cheRNA synthesis to promoters of proximal target genes.

Structure determination and functional analyses of budding yeast Rif1 reveal a novel, hooked N-terminal DNA-binding domain required for telomere maintenance and checkpoint control and show that Rif1's role in DNA-repair pathway choice is conserved in yeast and mammalian cells.

Two new studies show that RNA-binding proteins can mediate distinct and beneficial effects to cells by binding to the extensive double-stranded RNA (dsRNA) structures of inverted-repeat Alu elements (IRAlus). One study reports stress-induced export of the 110-kDa isoform of the adenosine deaminase acting on RNA 1 protein (ADAR1p110) to the cytoplasm, where it binds IRAlus so as to protect many mRNAs encoding anti-apoptotic proteins from degradation. The other study demonstrates that binding of the nuclear helicase DHX9 to IRAlus embedded within RNAs minimizes defects in RNA processing.

Interaction with heterotrimeric G proteins is a hallmark of G-protein-coupled receptor (GPCR) family members, and it is the key step for a diverse range of cell-signaling cascades. A recent cryo-EM structure of the human calcitonin receptor (CTR) in complex with a G-protein heterotrimer reveals novel insights into receptor–G-protein coupling.

Chromatin remodelers are ATP-driven enzymes that can slide nucleosomes along DNA. Chen and colleagues present a tantalizing ∼4-Å view of the SWI/SNF ATPase motor bound to the nucleosome, which offers novel structural clues into the remodeling process.

The spatial organization of the genome profoundly influences how genes are regulated in normal development or dysregulated in disease. A new study of the murine HoxB locus illustrates how promoter interactions direct higher-order chromatin folding.

The number of conferences on epigenetics has been increasing in the past decade, underscoring the impact of the field on a variety of areas in biology and medicine. However, the mechanistic role of the epigenome in adaptation and inheritance, and how the environment may impinge on epigenetic control, are topics of growing debate. Those themes were the focus of the inaugural international King Abdullah University of Science and Technology (KAUST) Research Conference on Environmental Epigenetics in Saudi Arabia, where more than 100 participants from 19 countries enjoyed vibrant scientific discussions and a pleasant February breeze from the Red Sea.

The DNA-adenine modification 6mA has recently been identified in metazoans. This Perspective summarizes the latest discoveries and suggests potential functional roles for 6mA in metazoan genomes.

Crystal structures of hGPR40, a target for treatment of type 2 diabetes, bound to a partial and an allosteric agonist explain the binding cooperativity between these ligands and present new opportunities for structure-guided drug design.

Microprocessor components Dgcr8 and Drosha associate with transcriptionally active coding and noncoding genes in a Mettl3-dependent manner and, upon temperature stress, relocate to heat-shock genes, where they mark mRNAs for subsequent degradation.

MDM2 mutations that prevent E2–ubiquitin binding without altering RING domain structure lead to loss of E3-ligase activity, while the ability to limit p53 transcriptional activity is retained, allowing cells to respond more quickly to cellular stress.