Articles in 2009

Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.

Successive rounds of selection of an RNA library in a mouse cancer model resulted in the identification of an aptamer that specifically bound a cancer-associated protein, providing an in vivo approach for identifying RNA motifs that can reveal and potentially inhibit tumor-specific targets.

Spatial- and time-resolution FRET methods on single pre-translocation ribosome complexes reveal that aminoglycoside antibiotics inhibit translocation by altering structural and dynamic parameters to stabilize the binding of aminoacyl tRNAs to the classical A-site of the ribosome.

Allantoin catabolism provides nitrogen, carbon and energy for several species, but the biochemical route to these resources in some species was unclear. A multidimensional bioinformatic search across organisms has now led to the identification of two enzymes that complete the degradation pathway.

Quorum sensing refers to a signaling mechanism allowing the behavior of bacterial populations to be coordinated based on cell density. Physical isolation of individual bacterial cells revealed that a single bacterium can respond to quorum sensing signals resulting in genetic reprogramming and enhanced.

Errors in functional annotations can cause significant problems in later research. A new method to identify misannotations by analyzing the genomic context correlations corrects these errors, such as in the reassignment of genes now demonstrated to have roles in leucine and fatty acid degradation.

Binding of HIV-1 Nef to host cell membranes is a biphasic process that involves electrostatic curvature-sensitive Nef-lipid interactions followed by a slower formation of an amphipathic helix. Nef action on the membrane may promote curvature and subsequent endocytosis of the host-cell proteins.

Synthetic biologists aim to rationally design and construct useful biological circuits. However, perturbation of host cell physiology, through the very process of turning on an artificial circuit, can give rise to unexpected emergent behaviors, such as bistability.

Understanding how proteins function in isolation and in their native context requires a merging of molecular-level techniques that explore the interplay of protein structure and dynamics.

Few antimicrobial drugs function by directly targeting RNA. A small molecule that binds the hepatitis C viral genome by 'locking' in a particular RNA conformation to inhibit viral protein production suggests a new paradigm for drug design.

Membrane curvature sensing by amphipathic helices is an emergent property of the ensemble of molecules and membrane sites. New data suggest that individual molecules do not experience stronger binding to curved membranes.

Intrinsically disordered proteins (IDPs) are subject to ubiquitin-independent degradation, a default and passive process. We describe here a model wherein a group of 'nanny' proteins function to protect newly synthesized IDPs from degradation by default, thereby insuring their maturation into important regulatory molecules.

In their native environments, proteins perform their biological roles in highly concentrated viscous solutions and in complex networks with numerous partners. Yet for many years, the normal practice has been to purify a protein of interest in order to characterize its structural and functional properties. In this Commentary, we discuss how protein scientists are now tackling the theoretical and methodological challenges of studying proteins in their physiological context.