Envelope glycoproteins of human and simian immunodeficiency virus (HIV and SIV) undergo a series of conformational changes when they interact with receptor (CD4) and co-receptor on the surface of a potential host cell, leading ultimately to fusion of viral and cellular membranes. Structures of fragments of gp120 and gp41 from the envelope protein are known, in conformations corresponding to their post-attachment and postfusion states, respectively. We report the crystal structure, at 4 A resolution, of a fully glycosylated SIV gp120 core, in a conformation representing its prefusion state, before interaction with CD4. Parts of the protein have a markedly different organization than they do in the CD4-bound state. Comparison of the unliganded and CD4-bound structures leads to a model for events that accompany receptor engagement of an envelope glycoprotein trimer. The two conformations of gp120 also present distinct antigenic surfaces. We identify the binding site for a compound that inhibits viral entry.
The central complex is a prominent structure in the Drosophila brain. Visual learning experiments in the flight simulator, with flies with genetically altered brains, revealed that two groups of horizontal neurons in one of its substructures, the fan-shaped body, were required for Drosophila visual pattern memory. However, little is known about the role of other components of the central complex for visual pattern memory. Here we show that a small set of neurons in the ellipsoid body, which is another substructure of the central complex and connected to the fan-shaped body, is also required for visual pattern memory. Localized expression of rutabaga adenylyl cyclase in either the fan-shaped body or the ellipsoid body is sufficient to rescue the memory defect of the rut2080 mutant. We then performed RNA interference of rutabaga in either structure and found that they both were required for visual pattern memory. Additionally, we tested the above rescued flies under several visual pattern parameters, such as size, contour orientation, and vertical compactness, and revealed differential roles of the fan-shaped body and the ellipsoid body for visual pattern memory. Our study defines a complex neural circuit in the central complex for Drosophila visual pattern memory.
Genetically engineered tobacco (Nicotiana tabacum L.) with the ability to accumulate glycinebetaine was established. The wild type and transgenic plants were exposed to heat treatment (25-50 degrees C) for 4 h in the dark and under growth light intensity (300 mumol m(-2) s(-1)). The analyses of oxygen-evolving activity and chlorophyll fluorescence demonstrated that photosystem II (PSII) in transgenic plants showed higher thermotolerance than in wild type plants in particular when heat stress was performed in the light, suggesting that the accumulation of glycinebetaine leads to increased tolerance to heat-enhanced photoinhibition. This increased tolerance was associated with an improvement on thermostability of the oxygen-evolving complex and the reaction center of PSII. The enhanced tolerance was caused by acceleration of the repair of PSII from heat-enhanced photoinhibition. Under heat stress, there was a significant accumulation of H(2)O(2), O (2) (-) and catalytic Fe in wild type plants but this accumulation was much less in transgenic plants. Heat stress significantly decreased the activities of catalase, ascorbate peroxidase, glutathione reductase, dehydroascorbate reductase, and monodehydroascorbate reductase in wild type plants whereas the activities of these enzymes either decreased much less or maintained or even increased in transgenic plants. In addition, heat stress increased the activity of superoxide dismutase in wild type plants but this increase was much greater in transgenic plants. Furthermore, transgenic plants also showed higher content of ascorbate and reduced glutathione than that of wild type plants under heat stress. The results suggest that the increased thermotolerance induced by accumulation of glycinebetaine in vivo was associated with the enhancement of the repair of PSII from heat-enhanced photo inhibition, which might be due to less accumulation of reactive oxygen species in transgenic plants.
We demonstrate highly efficient avalanche multiphoton luminescence (MPL) from ordered-arrayed gold nanowires (NWs) with low time-average excitation intensity, Iexc (5.0-9.1 kW/cm2). The intensity of avalanche MPL, IMPL, is about 10(4) times larger than that of three-photon luminescence, the slope partial differential log IMPL/ partial differential log Iexc of avalanche MPL reaches as high as 18.3, and the corresponding polarization dependence of IMPL has a form of cos50 phip. The emission dynamics of avalanche MPL and three-photon luminescence are also studied comparatively. These observations indicate that the highly efficient avalanche MPL is attributed to the giant enhancement and coupling of longitudinal surface plasmon resonance of ordered-arrayed gold NWs.
HIV/SIV envelope glycoproteins mediate the first steps in viral infection. They are trimers of a membrane-anchored polypeptide chain, cleaved into two fragments known as gp120 and gp41. The structure of HIV gp120 bound with receptor (CD4) has been known for some time. We have now determined the structure of a fully glycosylated SIV gp120 envelope glycoprotein in an unliganded conformation by X-ray crystallography at 4.0 A resolution. We describe here our experimental and computational approaches, which may be relevant to other resolution-limited crystallographic problems. Key issues were attention to details of beam geometry mandated by small, weakly diffracting crystals, and choice of strategies for phase improvement, starting with two isomorphous derivatives and including multicrystal averaging. We validated the structure by analyzing composite omit maps, averaged among three distinct crystal lattices, and by calculating model-based, SeMet anomalous difference maps. There are at least four ordered sugars on many of the thirteen oligosaccharides.
A pyrrolyl-based triazolophane, incorporating CH and NH donor groups, acts as a receptor for the pyrophosphate anion in chloroform solution. It shows selectivity for this trianion, followed by HSO 4 -> H 2 PO 4 -> Cl -> Br -(all as the corresponding tetrabutylammonium salts), with NH-anion interactions being more important than CH-anion interactions. In the solid state, the receptor binds the pyrophosphate anion in a clip-like slot via NH and CH hydrogen bonds.Pyrophosphate detection has aroused interest in the scientific community not only because pyrophosphate is the product of ATP hydrolysis under cellular conditions, 1 but also because it could afford a means of effecting real-time DNA sequencing. 2 Pyrophosphate monitoring may also have a role to play in cancer research since this anion is involved in DNA replication catalyzed by DNA polymerase. 3 Pyrophosphate is also of interest as a larger, more highly charged analogue of inorganic phosphate (H 2 PO 4 -/HPO 4 2-), which has physiological relevance in energy storage and signal transduction, in addition to being a structural component in teeth and bones. 4 Not surprisingly, therefore, considerable effort has been devoted recently to the development of synthetic receptors that allow for the recognition, detection, or extraction of pyrophosphate and related species, such as inorganic phosphate. 5 Systems incorporating neutral or cationic NH hydrogen bond donor groups (e.g., pyrrole, indole, ammonium, and guanidinium) or cationic CH hydrogen bond donor motifs (e.g. imidazolium and triazolium) have been particularly effective in this regard. However, to the best of our knowledge, receptors with neutral CH H-bond donors have yet to be exploited for the purpose of pyrophosphate (or phosphate) anion recognition. CH bonds are present in the overwhelming majority (97%) of chemical compounds. 6 Nevertheless, it is only recently that the importance of CH H-bond in biological and artificial anion recognition has come to be appreciated. 7 In recent pioneering work, Flood and co-workers reported the synthesis and anion binding properties of [3 4 ]triazolophanes. These new macrocycles have a diameter of about 3.8 Å, and display a high affinity for the chloride ion. 7(c) On the basis of this and previous theoretical and experimental studies, 8 it was suggested that the strength of neutral, triazole-derived C-H···X -(X -= halide) bonds can approach those of more traditional NH donors, such as pyrrole. We thus considered it of interest to combine both these recognition motifs within the same macrocyclic framework. Here, we report the first such system, namely the calix[2]1,3-bis(pyrro-2-yl)(1,4)-1,2,3-triazolo-phane (1), and show that it acts as a highly effective receptor for the pyrophosphate anion, both in the solid state and in organic media. 9 Our findings, supported by theory, provide support for the conclusion that NH-anion bonding interactions are more important than CH-anion interactions.The synthesis of 1 is shown in Scheme 1. Using "click" chemistry cond...
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