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Maintaining energy homeostasis requires complex feedback across organs that is difficult to study in isolated systems. New research uses whole-organism screening to identify key regulators of fasting metabolism in zebrafish, including ligands for the mitochondrial transporter protein TSPO.
A major determinant of the ion flux rate through acetylcholine receptors is a ring of five residues, four glutamates and a glutamine, at the channel's cytoplasmic mouth. The glutamates adopt alternate rotamer conformations so that only two directly affect channel conductance.
Combinatorial protein engineering based on structural data and the differential expression of alternate second receptor chains for interleukin-4 (IL-4) is used to modify and tune cellular specificity on primary human cells.
Selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) is a proven methodology for in vitro RNA secondary structure analysis. The identification of a new acylating agent permits the use of SHAPE to probe folded RNAs within living cells.
Stabilization of ubiquitin's β1-β2 region by computational design and phage display, targeting both buried and surface residues, yields a ubiquitin variant that specifically inhibits the deubiquitinase USP7 in vitro and in cells.
The human genome contains stretches of DNA sequence with unknown function. Peptidomics coupled to RNA-Seq now reveals a class of short open reading frames in human genomes that are translated into small peptides.
Medium-sized ring structures can provide unique entry points into natural product–like chemical space but are synthetically challenging to access. A biologically inspired method eases these challenges, employing a dearomatization-rearomatization sequence to form a diverse library of rings from tailored bicyclic compounds.