Articles in 2010

GNF-2 is a recently discovered, selective allosteric Bcr–Abl inhibitor. Solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry are now used to show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. The results show that the combination of allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.

The earliest body fossils of tetrapods (vertebrates with limbs rather than paired fins) date to the Late Devonian period. There have been claims of tetrapod trackways predating these body fossils but the age and identity of the track makers have remained controversial. The discovery of well-preserved and securely dated tetrapod tracks from Polish marine tidal flat sediments of early Middle Devonian age, around 18 million years older than the earliest tetrapod body fossils, is now presented.

Although Archaea encode proteasomes highly related to those of eukaryotes, archaeal ubiquitin-like proteins are less conserved and not known to function in protein conjugation, complicating our understanding of the origins of ubiquitination. Two small archaeal modifier proteins, SAMP1 and SAMP2, structurally similar to ubiquitin, are now reported to form protein conjugates in the archaeon Haloferax volcanii.

The differentiation of an embryonic stem cell (ESC) requires both suppression of the self-renewal process and activation of the specific differentiation pathway. The let-7 family of microRNAs (miRNAs) are now shown to suppress the self-renewal program in cells that are normally unable to silence this program, whereas introduction of ESC cell cycle regulating miRNAs blocks the action of let-7. Thus, the interplay between these two groups of miRNAs dictates cell fate.