Volume 4 Issue 8, August 2008

Cooperative binding effects pervade biology. Only a few basic principles are at play, but in different biological contexts cooperativity appears in distinct guises to achieve different ends. Here I discuss some of the manifestations of cooperativity that are most important in biology and drug discovery as they pertain to systems at different levels of complexity and also highlight aspects of this broadly important phenomenon that remain poorly understood.

The development of single-molecule tools has significantly impacted the way we think about biochemical processes. Watching a single protein in action allows us to observe kinetic details and rare subpopulations that are hidden in ensemble-averaging techniques. I will discuss here the pros and cons of the single-molecule approach in studying ligand binding in macromolecular systems and how these techniques can be applied to characterize the behavior of large multicomponent biochemical systems.

A new web portal helps connect scientists and coordinate scientific efforts to address the challenges of the developing world.

Phosphorylation and glycosylation of the tau protein, which is implicated in neurodegenerative diseases, are intimately linked. In vivo pharmacological inhibition of tau deglycosylation may be a new way to suppress abnormal tau phosphorylation, known to be involved in the formation of neurofibrillary tangles in the brain.

A stochastic view of allostery is providing quantitative estimates of the energy made available through protein photoswitches.

Analysis of individual RNA folding reactions reveals that, as in proteins, cooperative interactions selectively drive RNA toward its biologically active, native conformation. This new work establishes a platform for future investigations of the physical principles underlying the assembly of large RNA enzymes.

Many of the phenotypes shown by bacteria at high population densities are only beneficial when they are associated with eukaryotic hosts. A new study confirms that some bacteria may couple quorum sensing to host-derived signals to refine such interactions.

Transporter proteins mediate the import of nutrients and the export of toxins across biological membranes. A new crystal structure of a bacterial ABC transporter reveals an unexpected mechanism for transporter inhibition by its transported substrate.

New mechanistic insights are extending our understanding of cooperativity in biochemical processes. In this issue, we feature a collection of articles highlighting current research and future challenges in exploring cooperative systems in chemistry and biology.