Volume 7 Issue 5, May 2011

A small subpeptide from the tumor suppressor p53 is shown to mediate aggregation that is similar to that of amyloids. The result is nucleated assembly by mutant p53 that can abrogate function of wild-type p53 and its two functionally important homologs.

Classical cannabinoid receptors do not mediate all actions of the active drug in cannabis, THC. Here the mechanism by which THC enhances glycine receptor activity has been identified and used to design new pain therapeutics that avoid THC's adverse effects.

Parathyroid hormone analog PTH(1–34), used clinically to treat osteoporosis, forms a stable complex with its receptor and prolongs cAMP production even after internalization and recruitment to endosomes. New data suggest this signaling cascade is stimulated by β-arrestins and terminated by retromer.

Directed evolution of nucleic acids and proteins in the laboratory can produce many novel phenotypes in a relatively short time frame. A significant enhancement to these techniques allows continuous evolution in special turbidostats and can speed the discovery of proteins with desirable activities.

A selective, short-acting agonist for the sphingosine-1-phosphate receptor S1P₁ and GFP-S1P₁ knock-in mouse model are used to show that both receptor degradation and receptor reserve underlie the mechanisms of lymphocyte sequestration by agonists.

The ribosomal production of two short peptides conserved across divergent plant species unexpectedly uses an open reading frame for an unrelated protein, albumin, as well as albumin processing–machinery to create mature cyclic sequences.

Experiments on reconstituted liposomes and sperm capacitation, an activation process involving the reduction in membrane cholesterol content and subsequent exposure of surface carbohydrate, show that cholesterol masks the presentation of glycolipid head groups by inducing a conformational shift in the glycan moiety.

Magic-angle spinning ssNMR used to monitor the E. coli integral membrane protein DGK reconstituted into lipid bilayers reveals the kinetics and mechanisms of this enzyme in both the membrane phase where diacylglycerol is converted to PA and in the aqueous phase where ATP is converted to ADP.

Metabolic engineering often involves the addition of enzymes, redirection of metabolic flux or elimination of undesirable endpoints and thus requires laborious optimization of numerous parameters. A new method to derive 'blueprints' from real-time measurements of metabolic networks significantly accelerates this process as demonstrated with the production of dihydroxyacetone phosphate.

Going against the classical model of β-arrestin–mediated internalization and downregulation of GPCRs, FRET, FRAP and time-lapse imaging show that PTHR remains active when bound to β-arrestin and is ultimately terminated by retromer complex, a complex involved in transport from endosomes to the Golgi.

Mutant p53 can attenuate the function of wild-type p53, p63 and p73. An aggregation-nucleating sequence in p53 that is revealed in structurally destabilized mutants can induce coaggregation with p63 and p73, resulting in their sequestration in cellular inclusions.

Cannabis-induced analgesia results from potentiation of the α1 and α3 glycine receptors via a specific interaction with a transmembrane segment of the receptors, and this distinguishes the analgesic effects from the psychoactive effects of cannabinoids.

Synthesis of new vancomycin-like glycopeptides offers opportunities to overcome antibiotic resistance. The crystallographic identification of a reaction intermediate close to the surface of a glycopeptide tailoring enzyme leads to a new biocatalytic strategy to create two classes of teicoplanin analogs.

Hydrogenases can generate hydrogen gas, but oxygen sensitivity often limits their practical applications. Investigations of an oxygen-tolerant [NiFe] hydrogenase now show that an unusual FeS cluster with six cysteine ligands alters the electron pathway to reduce unwanted oxygen and maintain enzyme function.