Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor

The metabotropic glutamate receptors (mGluRs) are key receptors in the modulation of excitatory synaptic transmission in the central nervous system. Here we have determined three different crystal structures of the extracellular ligand-binding region of mGluR1--in a complex with glutamate and in two unliganded forms. They all showed disulphide-linked homodimers, whose 'active' and 'resting' conformations are modulated through the dimeric interface by a packed alpha-helical structure. The bi-lobed protomer architectures flexibly change their domain arrangements to form an 'open' or 'closed' conformation. The structures imply that glutamate binding stabilizes both the 'active' dimer and the 'closed' protomer in dynamic equilibrium. Movements of the four domains in the dimer are likely to affect the separation of the transmembrane and intracellular regions, and thereby activate the receptor. This scheme in the initial receptor activation could be applied generally to G-protein-coupled neurotransmitter receptors that possess extracellular ligand-binding sites.     

Evolution of the Sun's large-scale magnetic field since the Maunder minimum

The most striking feature of the Sun's magnetic field is its cyclic behaviour. The number of sunspots, which are dark regions of strong magnetic field on the Sun's surface, varies with a period of about 11 years. Superposed on this cycle are secular changes that occur on timescales of centuries and events like the Maunder minimum in the second half of the seventeenth century, when there were very few sunspots. A part of the Sun's magnetic field reaches out from the surface into interplanetary space, and it was recently discovered that the average strength of this interplanetary field has doubled in the past 100 years. There has hitherto been no clear explanation for this doubling. Here we present a model describing the long-term evolution of the Sun's large-scale magnetic field, which reproduces the doubling of the interplanetary field. The model indicates that there is a direct connection between the length of the sunspot cycle and the secular variations.     

Direct imaging of the pores and cages of three-dimensional mesoporous materials

Mesostructured composite materials, with features ranging from 20 to 500 A in size, are obtained by the kinetically controlled competitive assembly of organic and inorganic species into nanostructured domains. Short-range order is limited, and long-range order is determined by weak forces such as van der Waals or hydrogen-bonding. Three-dimensional mesoporous materials obtained by removing the organic phase are of particular interest for applications such as catalysis and chemical sensing or separation, for which structural features such as cavity shape, connectivity and ordered bimodal porosity are critical. But atomic-scale structural characterization by the usual diffraction techniques is challenging for these partially ordered materials because of the difficulty in obtaining large (> 10 microm) single crystals, and because large repeat spacings cause diffraction intensities to fall off rapidly with scattering angle so that only limited small-angle data are available. Here we present a general approach for the direct determination of three-dimensional mesoporous structures by electron microscopy. The structure solutions are obtained uniquely without pre-assumed models or parametrization. We report high-resolution details of cage and pore structures of periodically ordered mesoporous materials, which reveal a highly ordered dual micro- and mesoscale pore structure.     

Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex

F-box proteins are members of a large family that regulates the cell cycle, the immune response, signalling cascades and developmental programmes by targeting proteins, such as cyclins, cyclin-dependent kinase inhibitors, IkappaBalpha and beta-catenin, for ubiquitination (reviewed in refs 1-3). F-box proteins are the substrate-recognition components of SCF (Skp1-Cullin-F-box protein) ubiquitin-protein ligases. They bind the SCF constant catalytic core by means of the F-box motif interacting with Skp1, and they bind substrates through their variable protein-protein interaction domains. The large number of F-box proteins is thought to allow ubiquitination of numerous, diverse substrates. Most organisms have several Skp1 family members, but the function of these Skp1 homologues and the rules of recognition between different F-box and Skp1 proteins remain unknown. Here we describe the crystal structure of the human F-box protein Skp2 bound to Skp1. Skp1 recruits the F-box protein through a bipartite interface involving both the F-box and the substrate-recognition domain. The structure raises the possibility that different Skp1 family members evolved to function with different subsets of F-box proteins, and suggests that the F-box protein may not only recruit substrate, but may also position it optimally for the ubiquitination reaction.     

Distinct functions of the two isoforms of dopamine D2 receptors

Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse. D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia. By a mechanism of alternative splicing, the D2 receptor gene encodes two molecularly distinct isoforms, D2S and D2L, previously thought to have the same function. Here we show that these receptors have distinct functions in vivo; D2L acts mainly at postsynaptic sites and D2S serves presynaptic autoreceptor functions. The cataleptic effects of the widely used antipsychotic haloperidol are absent in D2L-deficient mice. This suggests that D2L is targeted by haloperidol, with implications for treatment of neuropsychiatric disorders. The absence of D2L reveals that D2S inhibits D1 receptor-mediated functions, uncovering a circuit of signalling interference between dopamine receptors.     

Organoplatinum crystals for gas-triggered switches

Considerable effort is being devoted to the fabrication of nanoscale devices. Molecular machines, motors and switches have been made, generally operating in solution, but for most device applications (such as electronics and opto-electronics), a maximal degree of order and regularity is required. Crystalline materials would be excellent systems for these purposes, as crystals comprise a vast number of self-assembled molecules, with a perfectly ordered three-dimensional structure. In non-porous crystals, however, the molecules are densely packed and any change in them (due, for example, to a reaction) is likely to destroy the crystal and its properties. Here we report the controlled and fully reversible crystalline-state reaction of gaseous SO2 with non-porous crystalline materials consisting of organoplatinum molecules. This process, including repetitive expansion-reduction sequences (on gas uptake and release) of the crystal lattice, modifies the structures of these molecules without affecting their crystallinity. The process is based on the incorporation of SO2 into the colourless crystals and its subsequent liberation from the orange adducts by reversible bond formation and cleavage. We therefore expect that these crystalline materials will find applications for gas storage devices and as opto-electronic switches.     

Nitride semiconductors free of electrostatic fields for efficient white light-emitting diodes

Compact solid-state lamps based on light-emitting diodes (LEDs) are of current technological interest as an alternative to conventional light bulbs. The brightest LEDs available so far emit red light and exhibit higher luminous efficiency than fluorescent lamps. If this luminous efficiency could be transferred to white LEDs, power consumption would be dramatically reduced, with great economic and ecological consequences. But the luminous efficiency of existing white LEDs is still very low, owing to the presence of electrostatic fields within the active layers. These fields are generated by the spontaneous and piezoelectric polarization along the [0001] axis of hexagonal group-III nitrides--the commonly used materials for light generation. Unfortunately, as this crystallographic orientation corresponds to the natural growth direction of these materials deposited on currently available substrates. Here we demonstrate that the epitaxial growth of GaN/(Al,Ga)N on tetragonal LiAlO2 in a non-polar direction allows the fabrication of structures free of electrostatic fields, resulting in an improved quantum efficiency. We expect that this approach will pave the way towards highly efficient white LEDs.     

Earthquake-induced changes in a hydrothermal system on the Juan de Fuca mid-ocean ridge

Hydrothermal vents on mid-ocean ridges of the northeast Pacific Ocean are known to respond to seismic disturbances, with observed changes in vent temperature. But these disturbances resulted from submarine volcanic activity; until now, there have been no observations of the response of a vent system to non-magmatic, tectonic events. Here we report measurements of hydrothermal vent temperature from several vents on the Juan de Fuca ridge in June 1999, before, during and after an earthquake swarm of apparent tectonic origin. Vent fluid temperatures began to rise 4-11 days after the first earthquake. Following this initial increase, the vent temperatures oscillated for about a month before settling down to higher values. We also observed a tenfold increase in fluid output from the hydrothermal system over a period of at least 80 days, extending along the entire ridge segment. Such a large, segment-wide thermal response to relatively modest tectonic activity is surprising, and raises questions about the sources of excess heat and fluid, and the possible effect on vent biological communities.     

The accelerations of stars orbiting the Milky Way's central black hole

Recent measurements of the velocities of stars near the centre of the Milky Way have provided the strongest evidence for the presence of a supermassive black hole in a galaxy, but the observational uncertainties poorly constrain many of the black hole's properties. Determining the accelerations of stars in their orbits around the centre provides much more precise information about the position and mass of the black hole. Here we report measurements of the accelerations of three stars located approximately 0.005 pc (projected on the sky) from the central radio source Sagittarius A* (Sgr A*); these accelerations are comparable to those experienced by the Earth as it orbits the Sun. These data increase the inferred minimum mass density in the central region of the Galaxy by an order of magnitude relative to previous results, and localize the dark mass to within 0.05 +/- 0.04 arcsec of the nominal position of Sgr A*. In addition, the orbital period of one of the observed stars could be as short as 15 years, allowing us the opportunity in the near future to observe an entire period.