The RNA-mediated higher order assembly of TDP-43, a protein associated with neurodegenerative diseases, preserves its solubility by reducing the risk of multivalent interactions between low complexity domains.
Quantitative time-resolved crosslinking mass spectrometry is developed to monitor protein interactions and dynamics inside molecular condensates and used to identify misfolding of the RNA-binding domain of FUS as a key driver of condensate-aging.
Defective mitochondrial protein import results in protein aggregation and a specific chaperone response in the cytosol, causatively linking mitochondrial function and cellular protein homeostasis disturbances observed in neurodegeneration.
Chromatin/transcriptome profiling in multiple mouse models with mutations in epigenetic machinery (EM) reveals shared abnormalities including many IgA-relevant genes, indicating that this kind of joint analysis may elucidate the multigenic nature of EM disorders.
Computational methods reveal how mutations affect the conformational landscape of the kinase domain of EGFR resulting in abnormal signaling and provide a structural framework for ongoing drug discovery efforts on mutant-specific EGFR inhibition.
The solubility product, a thermodynamic concept classically applied to poorly soluble ionic solutes, can rationalize the concentration dependence for liquid-liquid phase separation of multicomponent multivalent molecules.