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Efficient transport by single two-headed motor proteins requires coordination of the motor domains. A new single-molecule study sheds light on an important coordination mechanism by demonstrating an asymmetric strain dependence of the weak-to-strong binding transition in myosin-VI heads.
A class of proteins containing domains that are evolutionarily conserved among prokaryotes and eukaryotes was recently found to mediate post-translational AMP addition—a new protein modification called AMPylation. Similarities to the post-translational modification phosphorylation suggest that AMPylation may be an important regulatory mechanism.
Small-molecule inhibitors can induce phosphorylation priming of AGC kinases. Priming by ATP binding pocket conformation, rather than intrinsic kinase activity, has significant implications for drug discovery and therapeutic efficacy.
In the realm of modern drug discovery technologies, fragment-based approaches and virtual ligand screening are emerging alternative approaches to high-throughput screening (HTS). For as simple as it sounds, a hybrid approach in which fragments are discovered first in silico may be an unbeatable route to hit identification for some drug targets.
A high-throughput one-hybrid screen identifies a regulator of the Arabidopsis thaliana circadian gene CIRCADIAN CLOCK ASSOCIATED1 (CCA1). CCA1 HIKING EXPEDITION (CHE) represses CCA1 and physically interacts with TIMING OF CAB1 (TOC1) to link TOC1 with CCA1 in the clock.
SGS3 is essential for antiviral silencing and the biogenesis of several classes of siRNAs in plants, but until now no biochemical function has been ascribed to it. Both SGS3 and a viral suppressor of RNA silencing have now been shown to selectively bind 5′ overhang–containing dsRNA, implicating this RNA as a new intermediate in the RNA silencing pathway.
Jasmonates are important in defending plants against pathogens and in reproductive development. New evidence resolves the stereochemistry of the bioactive jasmonate hormone and suggests a chemical mechanism for modulating levels of the bioactive molecule in plants.
Labeling endogenous proteins in their natural environment with synthetic probes represents a major challenge in chemical biology. In a recent study, an elegant traceless labeling technique has been reported that allows attachment of biophysical probes to the targeted proteins in vivo.
Small-molecule library screening identifies simple imitators of the cellular signaling events that normally guide formation of the pancreas and its insulin-secreting beta cells, further enabling detailed analysis in vitro, or eventual diabetes therapies via large-scale differentiation of human stem cells.
Protein prenylation plays a key role in the localization and function of many proteins, but the number and identities of prenylated proteins are unknown. A new study uses a multidisciplinary approach to provide a broad yet detailed snapshot of prenylation within the mammalian proteome.