Articles in 2011

A growing body of evidence points to the importance of microcolonies in the dissemination of bacteria, yet there is a dearth of tools for systematically assessing the behavior of cells within such communities. New strategies for landscaping three-dimensional culture environments on microscopic scales may have a critical role in revealing how bacteria orchestrate antibiotic resistance and other social behaviors within small, dense aggregates.

Despite our continued efforts to assert control over pathogens, more and more bacteria are saying “no” to drugs. It is becoming increasingly apparent that microbial environments, influenced by intracellular and extracellular metabolic processes, modulate antibiotic susceptibility in bacteria. A deeper understanding of these environmental processes may prove crucial for the development of new antibacterial therapies.

The distinction between different cell-envelope architectures has defined much of our thinking about bacterial systematics, but the evolution of different envelope layers has been harder to understand. A recent publication focused on the non-model organism Acetonema longum provides important clues to the possible origin of the second membrane typical of Gram-negative bacteria.

Antibiotics promote the spread of resistance in the clinic, but various mechanisms may exist in natural environments that tilt the balance toward antibiotic sensitivity. Studying such mechanisms could help us understand the evolutionary dynamics of resistance and sensitivity in the wild, which may inspire new therapeutic strategies.

A sensitive probe that detects protein sulfenylation in cells reveals that sulfenylation of the active site cysteine in EGFR enhances its kinase activity.

Biochemical and bioinformatic analyses have pointed to crotonyl-CoA carboxylase-reductase homolog as responsible for introducing unusual extender units into polyketide pathways; structural and mutational analysis now defines the basis for this reaction and the mechanism for substrate discrimination.

Enzymes that act on inositol pyrophosphates must accommodate a densely charged substrate while retaining excellent substrate specificity to control downstream signaling networks. Structural and biochemical data now define the basis for substrate recognition and the reaction coordinate for formation of a high-energy pyrophosphate bond.

DNA polymerases contain two cysteine-rich metal binding motifs (CysA and CysB), which have been assigned as zinc-ion binding sites by structural studies. A combination of biochemical and spectroscopic techniques reveal that the CysB site of yeast B-family polymerases binds a [4Fe-4S] cluster that is essential for polymerase function.

Lysophosphatidic acid (LPA), a lipid that induces neuropathic pain, functions by binding directly to the ion channel TRPV1 independently from the G protein–coupled receptors that generally mediate LPA function.

Single-molecule studies on a molecular motor F₁-ATPase provide evidence that energy from catalysis is gradually converted to mechanical rotation, explaining the high efficiency of energy conversion and the mechanism for positive cooperativity among subunits during ATP hydrolysis.

An intramolecular cleft of the FAK FERM domain mediates interaction with sarcomeric myosin. Chemical cross-linking, SAXS and mutational analyses confirm the interaction, and inhibiting the interaction with a peptide activates FAK and promotes the cardiomyocyte hypertrophic response.

An orcein-related small molecule can drive polymerization of amyloid-β, implicated in Alzheimer's disease, without remodeling oligomeric or fibril forms but by stabilizing a seeding-competent protofilament state and shortening the lag phase of spontaneous polymerization.