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Heterodimerization of G protein–coupled receptors can lead to the activation of intracellular pathways that are not triggered by either of the individual receptors. This property may lead to the development of new therapeutic approaches showcasing increased efficiency and selectivity.
The demonstration of excitation energy dissipation via energy transfer in a cyanobacterial chlorophyll-carotenoid membrane complex provides evidence that this mechanism may also operate in the light-harvesting complex antennae of higher plants.
Bacterial translation elongation factor P (EF-P) is essential to overcome ribosome stalling at polyproline stretches during protein synthesis. A new mechanism of EF-P activation, identified in a subset of Bacteria, involves addition of the sugar L-rhamnose to a critical arginine residue.
This Perspective discusses recent advances in understanding the structural and pharmacological properties of the downstream Hedgehog pathway effector Smoothened. Small molecule agonists and antagonists of Smo could be used as potential therapeutics.
Cytosolic proteins can be modified cotranslationally by the installation of O-GlcNAc groups onto serine and threonine residues. This modification suppresses cotranslational ubiquitination and stabilizes proteins against proteasomal degradation.
O-GlcNAcylation is a known post-translational modification, but analysis of nascent proteins now demonstrates that it also occurs during translation, preventing proteolytic degradation of modified proteins by blocking ubiquitination.
Several GPCRs have ligands that act as pharmacological chaperones that rescue function of mutated receptors. This formed the basis of a screening strategy to identify new ligands for Frizzled4 that act allosterically at an effector domain to inhibit β-catenin signaling.
Establishing the existence of a Diels-Alderase—an enzyme that catalyzes a concerted [4 + 2] cycloaddition—is made easier by a crystal structure of SpnF, which, along with computational and biochemical analysis, should enable mechanistic investigations.
The discovery of two new types of enzymes that act in tandem within the spirotetramate biosynthetic pathway to catalyze [4+2] cycloadditions offers new opportunities for mechanistic investigations of potential Diels-Alderases.
Technologies that bias GPCR expression for formation of heterodimers show that, when heterodimerized, α2C-AR and AT-1R exhibit atypical Gs-cAMP-PKA signaling upon ligand stimulation compared to either parent receptor expressed alone and mimic activation associated with arterial hypertension.
Light-harvesting complexes (LHCs) manage energy flux into photosynthesis and dissipate excess light energy. The demonstration of dissipative energy transfer from chlorophyll-a to β-carotene in cyanobacterial high light–inducible proteins provides a mechanistic model for similar processes in LHCs.