Volume 11 Issue 1, January 2015

AAA+ proteases are quality control machineries consisting of substrate-binding ATPase modules for protein unfolding and a proteolytic chamber. New research now shows a redox switch in the Escherichia coli Lon protease that controls this process, widening the exit pore and activating proteolysis during transition from anaerobic to aerobic environments.

Hydrogen peroxide regulates cell signaling pathways through oxidation of specific thiol proteins. A new study describes a relay system involving peroxiredoxin 2 as a peroxide sensor that oxidizes the mammalian transcription factor STAT3 via a mixed disulfide intermediate.

The ubiquitin-conjugating enzyme Ube2w monoubiquitinates proteins with disordered N termini and may target lysine-less proteins for degradation.

Understanding how tumor cells utilize metabolic pathways for proliferation may provide useful strategies for combating cancer. A Perspective discusses recent advances in cancer drug development that target specific aspects of mitochondrial biosynthesis and bioenergetics processes.

PimA provides an unusual example of conformational flexibility: structural, biophysical and disulfide trapping experiments now show a glycosyltransferase involved in tuberculosis virulence undergoes a major rearrangement upon contact with membranes.

The α1-adrenergic receptor antagonist terazosin protects flies and mammalian cells from stress and apoptosis through direct activation of the glycolytic enzyme phosphoglycerate kinase 1, which interacts with Hsp90 to promote ATP consumption.

A crystal structure of a chimera composed of lipid-metabolizing transmembrane enzymes HRASLS3 and LRAT (which catalyzes esterification of vitamin A) identifies a quaternary structural rearrangement that coincides with formation of a three-dimensionally swapped dimer.

Inhibitors of FKBP51 with antidepressive activity are selective over the related FKBP52 and bind FKBP51 by an induced-fit mechanism that causes a conformational change. The analogous conformational change in FKBP52 generates a strained conformation.

Bacterial MreB forms cytoskeletal filaments, rotating around the cell width, helping to shape cells. Imaging experiments indicate that MreB association with the B. subtilis cell membrane requires the peptidoglycan and wall teichoic acid precursor lipid II.

Proteolysis must be carefully controlled to degrade desired targets without causing cellular damage. New data show that Lon protease in Enterobacteriaceae is regulated by a redox-dependent disulfide bond that determines the size of its exit pore.

Biochemical, bioinformatic and genetic evidence uncover a tyrosine biosynthesis pathway in plants that—in contrast to known plant pathways—occurs in the cytosol, is insensitive to tyrosine feedback regulation and uses the traditionally bacterial prephenate dehydrogenase.

The loss of GSK-3 activity alters cellular responsiveness to kinase inhibitors such as mTOR and PLK1. A kinome-wide RNAi screen reveals that GSK-3 interacts with a third of known kinases.

A redox relay was identified in mammalian cells where the H₂O₂-reactive protein peroxiredoxin-2 oxidizes the transcription factor STAT3, resulting in the formation of transcriptionally inactive disulfide-linked oligomers.

Peptide natural product backbones are typically made ribosomally or by NRPS machinery. Exploration of pheganomycin biosynthesis defines a third hybrid model in which a grasp ligase joins an NRPS product with a ribosomally produced peptide.

The structure of complement regulatory protein factor H in complex with a preferred sialylated trisaccharide and the C3b thioester domain supports the idea of a ternary complex that mediates discrimination between self and nonself in a branch of innate immunity.

An NMR structure reveals that the C terminus of the ubiquitin-conjugating enzyme Ube2w is disordered, leading to specific pairings with disordered substrates; loss of this sequence causes decreased substrate binding and ubiquitin transfer activity.