Recommended Reads
Check in each week for recommendations on new, interesting, and ground-breaking research!
Molecular chaperones bind to unfolded proteins to assist in their folding and limit aggregation. Recent studies using NMR spectroscopy reveal how diverse chaperone classes interact with their client proteins. Here, Arhar et al. review the similarities and differences between four example chaperones: Spy, Trigger Factor, DnaK and HscA–HscB. These chaperones all bind clients with relatively weak affinity, driving clients toward the stronger interactions of the folded state. However, the mechanisms of client release and ATP cycling differ greatly between chaperones.
In obesity, adipose tissue dysfunction contributes to metabolic complications and insulin resistance. Adipose tissue-specific gene expression is influenced by interactions with cis-regulatory elements, with effects on three-dimensional chromosome conformation. Recent advances reveal that in adipose tissue, cis-regulatory elements are linked to chromosome architecture. Here, Park et al. review epigenomics in adipose tissue rewiring, focusing on the role of DNA methylation and its significance in disease pathology.
Heart contraction is powered by cardiac myosin, a molecular motor that generates heart power output to meet the needs of the body. Recent studies show that myosin actively regulates cardiac contraction through complex regulatory mechanisms. Furthermore, tension generated by myosin contributes to additional physiological processes. Here, Barrick and Greenberg review myosin-based force generation and mechanotransduction in disease and development. They also discuss the discovery of therapeutics that target cardiac myosin and some remaining questions surrounding myosin function.
Mitophagy is a selective form of autophagy that regulates the bulk clearance of mitochondria, critical organelles in eukaryotes. Ubiquitin-independent mitophagy, observed in yeast and some developing metazoan cells, is mediated by phosphorylation of mitochondria-anchored autophagy receptors. During conditions of stress, when oxidative damage is possible, ubiquitin-dependent mechanisms recruit cytosolic autophagy receptors. The mitochondrial kinase PINK1 regulates a ubiquitin-dependent mitophagy pathway via recruitment of the ubiquitin ligase parkin. Here, Terradas et al.review mitophagy mechanisms with a focus on the role of post-translational modifications.
Type 2 diabetes (T2D) involves β-cell dysfunction and incomplete compensation for insulin resistance and affected one in 10 Americans in 2020. Insulin resistance affects glucose uptake via glucose transporter type 4 (GLUT4) and is the primary defect preceding T2D. In previous work, Reilly and collaborators generated an insulin-resistant mouse model with human GLUT4 promoter-driven insulin receptor knockout (GIRKO) in muscle, adipose and neuronal subpopulations. That research suggested there were additional factors and events leading to overt diabetes.
The pathogen Legionella pneumophila translocates effectors into its host using the Dot/Icm type IV secretion system (T4SS). Within the host, the bacteria affect processes including organelle trafficking, inflammation, ubiquitination and apoptosis. The translocated effectors also contribute to virulence in a variety of ways, including interactions with one another. These effector–effector interactions establish a niche for the pathogen while maintaining homeostasis. Here, Iyer and Das review recent developments in the diverse biochemical mechanisms and structure–function relationships of Legionella effector pairs.
In this article, Ito et al. identify a complex comprising CNKSR2 and the guanine nucleotide exchange factor, CYTH2, necessary for proper neuron development in the mouse hippocampus. They show that CYTH2 binding prevents CNKSR2 degradation. In addition, silencing of CNKSR2 or CYTH2 affects their cellular localization. CNKSR2- and CYTH2-knockdown cells exhibit characteristics of immature granule cells —potentially involving these proteins in neuron differentiation. The authors conclude that CNKSR2 interaction with CYTH2 is necessary for proper cellular development within the hippocampus via the formation of a stabilization complex of these two proteins.
Designed ankyrin repeat proteins (DARPins) are antibody mimetics that mediate protein–protein interactions and are used as a tool for drug development. These proteins are simpler than immunoglobulins (IGs) and are an alternative to IG-derived binders. DARPins present a modular architecture with stacks of akyrin repeats flanked by N- and C-terminal capping repeats. For this research article, Schilling et al. performed in silico analysis and a rationally guided Ala-Scan and determined position 17 of the N-terminal capping repeat plays a key role in overall protein thermostability.
