Volume 22 Issue 12, December 2015

Polyglutamine (polyGln) expansions induce protein misfolding and aggregation into fibrillar deposits, which are believed to underlie forms of neurodegeneration through a mechanism involving gain of toxic function. Polyalalanine expansions are now shown to differ from polyGln in kinetics of aggregation, morphology of aggregates and mechanism of toxicity.

The mechanisms guiding the substrate specificity of kinases are still poorly understood. Two recent reports provide further insights into how the epidermal growth factor receptor (EGFR) tyrosine kinase recognizes targets by identifying a new consensus motif that requires a Src-mediated priming phosphorylation.

In this Perspective, the authors discuss how recent innovations in single-molecule fluorescence approaches now permit protein dynamics to be monitored in increasingly complex biological systems and cellular environments.

IgG4 antibodies can exchange Fab arms and show different affinities for Fc receptors than do other IgG subclasses. The structure of full-length pembrolizumab, a human IgG4 approved to treat advanced melanoma, provides a framework to understand IgG4's properties.

The SUMO E3 ligase ZNF451 is a representative member of a new class of SUMO enzymes that execute catalysis via tandem SUMO-interaction motifs, thus allowing efficient SUMO-chain formation.

Structural and biochemical analyses establish the catalytic mechanism of ZNF451, a new class of E3 ligases.

Single-particle electron microscopy reconstruction of the budding yeast replisome locates leading-strand Pol ε and lagging-strand Pol α on opposite sides of the CMG helicase and suggests a new DNA path through the complex during replication.

Preference of EGFR for substrates that are primed by prior phosphorylation provides the molecular explanation for integration of Src and EGFR signaling via Src-mediated phosphorylation of the adaptor protein Shc1.

Crystallographic, biophysical and in silico analyses indicate that the conformational state of the mechanosensitive channel MscS is determined by the reorganization, due to changes in membrane tension, of the lipids within and around the protein.

New data show that R loops differentially modulate binding of chromatin remodelers Tip60–p400 and PRC2 at coding and noncoding gene promoters of mouse ESCs and thereby control transcription and cellular differentiation.

In vitro and in vivo analyses show that the aggregation mechanism of polyalanine expansions is based on assembly into α-helical clusters with diverse oligomeric species, in contrast to that of polyglutamine expansions, which form amyloid fibrils.

Crystal structures of human heparanase in its apo form and bound to oligosaccharide substrates offer insights into the mechanism of substrate recognition and catalysis.

New crystal structures and supporting functional assays identify the p19 and p45 subunits of Tetrahymena telomerase as homologs of the Stn1 and Ten1 subunits of the CST complex, which coordinates telomere replication.

Comprehensive identification of mRNA-binding proteins in S. cerevisiae and C. elegans reveals their evolutionary conservation; strikingly, most components of the glycolytic pathway and proteasome are detected, thus possibly indicating an ancient mechanism for metabolic control.