Volume 25 Issue 6, June 2018

Activation signals from GPCRs, the largest receptor family, are transmitted to heterotrimeric G proteins and arrestins, and can be differentially modulated by GPCR phosphorylation. In a recent article, available data, including multiple arrestin structures, are analyzed to decipher common and state-specific conformational changes in arrestins and how these depend on patterns of receptor phosphorylation.

Rittinger and Walden review recent structural and functional insights to contrast and compare RBR E3 ubiquitin ligases and their regulation through autoinhibition, post-translational modifications, multimerization and protein-protein interactions.

Bhat and Cortez discuss current knowledge on the multiple mechanisms by which RPA and RAD51 contribute to genome stability during DNA replication, in particular for replication fork reversal and fork protection.

Kinetic and structural analyses show that the activity of two covalent inhibitors of human KRAS^G12C, which initially bind to a shallow pocket with low affinity, is driven by KRAS-mediated catalysis of the chemical reaction with Cys12.

Segments from TDP-43 LCD form irreversible steric zippers typical of amyloid fibrils and labile interactions found in reversible assemblies. Familial ALS mutations or a phosphorylation event can convert reversible to irreversible aggregates.

Structures of human C5aR in ternary complexes with the peptide antagonist PMX53 and a non-peptide antagonist, either avacopan or NDT9513727, reveal the orthosteric effects of PMX53, the allosteric effects of the non-peptide drugs and structural details of signal transduction by C5aR.

Single-molecule analyses using a DNA substrate with a bridge linker reveals a role of PAXX in molecular bridging of double-strand breaks to facilitate NHEJ-mediated repair.

Crystal structures of PAFR in complex with the antagonist SR 27417 and the inverse agonist ABT-491, together with accompanying experiments, provide insight into recognition of PAF and reveal an unusual ligand-dependent conformation of helical bundle.

Depletion, ChIP and Hi-C analyses of the genomic distribution of the two variant cohesin complexes in human cells reveal non-redundant functions and differential contributions to 3D genome organization.

The load-dependence of the detachment rate of single molecules of human β-cardiac myosin from actin, and the effects of small-molecule compounds and cardiomyopathy-causing mutations, are investigated using harmonic force spectroscopy.

A cryo-EM structure of the human SLC1 transporter ASCT2 in the inward-facing conformation reveals the retrovirus-docking site and helps to elucidate the transport cycle. The transport domain is more solvent exposed than in most of the homolog structures.

The crystal structure of SLC38A9 from Danio rerio in complex with arginine in the cytosol-open conformation reveals the mechanism of substrate binding.

Cryo-EM structures of F-actin captured in different nucleotide states, by using nucleotide analogs or small molecules, reveal different conformational states linked to ATP hydrolysis.

Analysis of 18 available structures and other data reveals a new, conserved structural motif in arrestins and suggests that different phosphorylation patterns of the GPCR C terminus can drive distinct arrestin conformations and functional outcomes.