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Synthetic organic chemistry of complex natural products and their substructures provides challenges for the chemist and invaluable tools for the biologist. The production of a 'GPI chip', a device for simultaneously measuring and characterizing antibody responses to GPI structures, is applied to dissect malaria-induced antibody responses.
An in-depth biophysical look at lipids in the influenza viral envelope reveals disordered membranes at physiological temperatures, and will likely reshape the debate over the role of lipids and proteins in biomembranes.
A20 protein, a regulator of inflammation and cell survival, modulates cellular signaling via two apparently opposite enzyme activities. Recent studies elucidate the unusual structural organization of the A20 protease domain and provide new mechanistic insights into its biological function.
Signaling via phosphorylation-regulated protein-protein interactions often involves flexible or unstructured proteins. Detailed biophysical and computational studies on one such interaction reveal a marvelously intricate, temporally regulated, multistep conduit for signal transduction in the cell cycle.
Crystallographic analysis has been instrumental in revealing the molecular basis for the pharmacological properties of several natural and synthetic ligands of steroid receptors, but it is often a long and arduous process. A new method for stabilizing these receptors greatly accelerates this process, allowing generation of apo receptor crystals and the comparison of multiple structures to define pathway-specific interactions.
Methylmalonyl coenzyme A mutase (MCM) catalyzes the adenosylcobalamin-dependent isomerization of methylmalonyl-CoA to succinyl-CoA. Adenosyltransferase, an enzyme that carries out the final step in biosynthesis of adenosylcobalamin, is shown to be involved in delivery of the cofactor to MCM.
Postsynthetic modifications are widespread in genetic regulation. Trm9-mediated modification of the anticodon wobble base of specific tRNAs modulates expression of DNA damage response mRNAs in which cognate codons are unusually overrepresented. Thus, modification-dependent tRNA decoding activity is keyed to codon use in a genetic program.
A novel biosensor developed to visualize phosphatidylserine in intact cells suggests a new role for the anionic lipid in specifying intracellular membranes involved in signaling events.
The escape of mature malaria parasites from the confines of their host red blood cells is an essential yet poorly understood process. Recent studies now highlight a key role for parasite proteases that trigger the degradation of parasite and host membranes, leading to the egress of infectious parasite forms.
The highly sensitive and artificial biochemical assays that enable high-throughput screening are vulnerable to artifact-generating compounds that occur in drug screening collections. An investigation of known aggregator compounds and amyloid fibrillization inhibitors suggests that such inhibitors operate via a nonspecific mechanism in a well-used assay of amyloid fibrillization.
Recent crystal structures of a bacterial copper tolerance protein reveal an intriguing copper binding site that includes tryptophan. Its close proximity coupled with spectroscopic data suggests an unusual cation-π interaction between Cu(I) and the aromatic ring of tryptophan.
Schizophrenia is thought to involve a dysfunction of glutamatergic and GABAergic signaling in the prefrontal cortex, but how these systems interact in the disease has been unclear. Now ketamine, a glutamatergic NMDA receptor antagonist, may provide a mechanism that could link these pathways.
