Protein folds: molecular systematics in three dimensions

Advances in methods of structure determination have led to the accumulation of large amounts of protein structural data. Some 500 distinct protein folds have now been characterized, representing one-third of all globular folds that exist. The range of known structural types and the relatively large fraction of the protein universe that has already been sampled have greatly facilitated the discovery of some unifying principles governing protein structure and evolutionary relationships. These include a highly skewed distribution of topological arrangements of secondary-structure elements that favors a few very common connectivities and a highly skewed distribution in the capacity of folds to accommodate unrelated sequences. These and other observations suggest that the number of folds is far fewer than the number of genes, and that the fold universe is dominated by a small number of giant attractors that accommodate large numbers of unrelated sequences. Thus all basic protein folds will likely be determined in the near future, laying the foundation for a comprehensive understanding of the biochemical and cellular functions of whole organisms.     

RGS2 regulates signal transduction in olfactory neurons by attenuating activation of adenylyl cyclase III

The heterotrimeric G-protein Gs couples cell-surface receptors to the activation of adenylyl cyclases and cyclic AMP production (reviewed in refs 1, 2). RGS proteins, which act as GTPase-activating proteins (GAPs) for the G-protein alpha-subunits alpha(i) and alpha(q), lack such activity for alpha(s) (refs 3-6). But several RGS proteins inhibit cAMP production by Gs-linked receptors. Here we report that RGS2 reduces cAMP production by odorant-stimulated olfactory epithelium membranes, in which the alpha(s) family member alpha(olf) links odorant receptors to adenylyl cyclase activation. Unexpectedly, RGS2 reduces odorant-elicited cAMP production, not by acting on alpha(olf) but by inhibiting the activity of adenylyl cyclase type III, the predominant adenylyl cyclase isoform in olfactory neurons. Furthermore, whole-cell voltage clamp recordings of odorant-stimulated olfactory neurons indicate that endogenous RGS2 negatively regulates odorant-evoked intracellular signalling. These results reveal a mechanism for controlling the activities of adenylyl cyclases, which probably contributes to the ability of olfactory neurons to discriminate odours.     

Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion

SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Rab-GTPases, together with their cofactors, mediate the attachment step in the membrane fusion of vesicles. But how bilayer mixing--the subsequent core process of fusion--is catalysed remains unclear. Ca2+/calmodulin controls this terminal process in many intracellular fusion events. Here we identify V0, the membrane-integral sector of the vacuolar H+-ATPase, as a target of calmodulin on yeast vacuoles. Between docking and bilayer fusion, V0 sectors from opposing membranes form complexes. V0 trans-complex formation occurs downstream from trans-SNARE pairing, and depends on both the Rab-GTPase Ypt7 and calmodulin. The maintenance of existing complexes and completion of fusion are independent of trans-SNARE pairs. Reconstituted proteolipids form sealed channels, which can expand to form aqueous pores in a Ca2+/calmodulin-dependent fashion. V0 trans-complexes may therefore form a continuous, proteolipid-lined channel at the fusion site. We propose that radial expansion of such a protein pore may be a mechanism for intracellular membrane fusion.     

Observation of coherent optical information storage in an atomic medium using halted light pulses

Electromagnetically induced transparency is a quantum interference effect that permits the propagation of light through an otherwise opaque atomic medium; a 'coupling' laser is used to create the interference necessary to allow the transmission of resonant pulses from a 'probe' laser. This technique has been used to slow and spatially compress light pulses by seven orders of magnitude, resulting in their complete localization and containment within an atomic cloud. Here we use electromagnetically induced transparency to bring laser pulses to a complete stop in a magnetically trapped, cold cloud of sodium atoms. Within the spatially localized pulse region, the atoms are in a superposition state determined by the amplitudes and phases of the coupling and probe laser fields. Upon sudden turn-off of the coupling laser, the compressed probe pulse is effectively stopped; coherent information initially contained in the laser fields is 'frozen' in the atomic medium for up to 1 ms. The coupling laser is turned back on at a later time and the probe pulse is regenerated: the stored coherence is read out and transferred back into the radiation field. We present a theoretical model that reveals that the system is self-adjusting to minimize dissipative loss during the 'read' and 'write' operations. We anticipate applications of this phenomenon for quantum information processing.     

A bizarre predatory dinosaur from the Late Cretaceous of Madagascar

Here we report the discovery of a small-bodied (approximately 1.8 m) predatory dinosaur from the Late Cretaceous (Maastrichtian) of Madagascar. Masiakasaurus knopfleri, gen. et sp. nov., represented by several skull elements and much of the postcranial skeleton, is unique in being the only known theropod with a highly procumbent and distinctly heterodont lower dentition. Such a derived dental morphology is otherwise unknown among dinosaurs. Numerous skeletal characteristics indicate that Masiakasaurus is a member of Abelisauroidea, an enigmatic clade of Gondwanan theropods. Previously, small-bodied abelisauroids were known only from Argentina. The occurrence of Masiakasaurus on Madagascar suggests that small-bodied abelisauroids, like their larger-bodied counterparts, were more cosmopolitan, radiating throughout much of Gondwana and paralleling the diversification of small coelurosaur theropods in Laurasia.     

Genome sequence of enterohaemorrhagic Escherichia coli O157:H7

The bacterium Escherichia coli O157:H7 is a worldwide threat to public health and has been implicated in many outbreaks of haemorrhagic colitis, some of which included fatalities caused by haemolytic uraemic syndrome. Close to 75,000 cases of O157:H7 infection are now estimated to occur annually in the United States. The severity of disease, the lack of effective treatment and the potential for large-scale outbreaks from contaminated food supplies have propelled intensive research on the pathogenesis and detection of E. coli O157:H7 (ref. 4). Here we have sequenced the genome of E. coli O157:H7 to identify candidate genes responsible for pathogenesis, to develop better methods of strain detection and to advance our understanding of the evolution of E. coli, through comparison with the genome of the non-pathogenic laboratory strain E. coli K-12 (ref. 5). We find that lateral gene transfer is far more extensive than previously anticipated. In fact, 1,387 new genes encoded in strain-specific clusters of diverse sizes were found in O157:H7. These include candidate virulence factors, alternative metabolic capacities, several prophages and other new functions--all of which could be targets for surveillance.