Proteolysis

Crystal structure of a rhomboid family intramembrane protease. Wang, Y. et al. Nature 11 Oct 2006 (doi: 10.1038/nature05255)

The Escherichia coli protein GlpG is a rhomboid-family protease that cleaves the transmembrane domain of membrane-protein substrates. The 2.1-Å crystal structure of the GlpG core domain, which consists of six transmembrane domains, provides new insights into the mechanism of intramembrane proteolysis. The catalytically active site of GlpG is embedded in the membrane, and the substrate is proposed to dock laterally between two transmembrane helices, replacing a loop structure that functions as a gate that blocks the lateral opening of the active site.

Membrane trafficking

Exomer: a coat complex for transport of select membrane proteins from the trans -Golgi network to the plasma membrane in yeast. Wang, C.-W. et al. J. Cell Biol. 174, 973–983 (2006)

Wang and colleagues uncovered a new type of coated vesicle that transports the yeast plasma-membrane protein Chs3 directly from the trans-Golgi network (TGN) to the plasma membrane of the mother–bud neck. Chs5 and Chs6, as well as three Chs6 paralogues, form a complex that is required for the transport of Chs3. Coat assembly is initiated by the activation of a G protein of the Arf family; indeed, Sec7 — a TGN-localized Arf1 nucleotide-exchange factor — is required to recruit Chs5 to the TGN surface. The coat complex was visualized by electron microscopy and was named exomer for its role in exocytosis from the TGN to the cell surface.

DNA repair

Direct observation of individual RecA filaments assembling on single DNA molecules. Galletto, R. et al. Nature 20 Sep 2006 (doi: 10.1038/nature05197)

Recombinational DNA repair in Escherichia coli involves the formation (or 'nucleation') of a RecA nucleoprotein filament on DNA, followed by elongation. Galletto et al. visualized filament assembly on individual double-stranded DNA molecules using fluorescently modified RecA. Nucleation of RecA filaments is independent of ATP hydrolysis but dependent on the type of nucleoside triphosphate and the RecA concentration. By contrast, individual RecA filaments can grow bidirectionally in the presence of ATP, and this growth is independent of the nucleoside triphosphate.

Mechanisms of disease

Caveolin-1 is essential for liver regeneration. Fernández, M. A. et al. Science 313, 1628–1632 (2006)

Caveolin-1 is an essential component of caveolae — distinct plasma-membrane domains that are involved in processes such as signalling and membrane sorting. Caveolin-1-knockout mice showed low survival and impaired liver regeneration after partial hepatectomy. This phenotype was associated with an intracellular lipid imbalance, reduction in lipid-droplet accumulation and a failure by cells to progress through the cell cycle. Caveolin-1 is therefore proposed to have an important role in coordinating lipid metabolism with the proliferative response during liver regeneration.