Structural and functional conservation of key domains in InsP3 and ryanodine receptors

Inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) are tetrameric intracellular Ca(2+) channels. In each of these receptor families, the pore, which is formed by carboxy-terminal transmembrane domains, is regulated by signals that are detected by large cytosolic structures. InsP(3)R gating is initiated by InsP(3) binding to the InsP(3)-binding core (IBC, residues 224-604 of InsP(3)R1) and it requires the suppressor domain (SD, residues 1-223 of InsP(3)R1). Here we present structures of the amino-terminal region (NT, residues 1-604) of rat InsP(3)R1 with (3.6??) and without (3.0??) InsP(3) bound. The arrangement of the three NT domains, SD, IBC-β and IBC-α, identifies two discrete interfaces (α and β) between the IBC and SD. Similar interfaces occur between equivalent domains (A, B and C) in RyR1 (ref. 9). The orientations of the three domains when docked into a tetrameric structure of InsP(3)R and of the ABC domains docked into RyR are remarkably similar. The importance of the α-interface for activation of InsP(3)R and RyR is confirmed by mutagenesis and, for RyR, by disease-causing mutations. Binding of InsP(3) causes partial closure of the clam-like IBC, disrupting the β-interface and pulling the SD towards the IBC. This reorients an exposed SD loop ('hotspot' (HS) loop) that is essential for InsP(3)R activation. The loop is conserved in RyR and includes mutations that are associated with malignant hyperthermia and central core disease. The HS loop interacts with an adjacent NT, suggesting that activation re-arranges inter-subunit interactions. The A domain of RyR functionally replaced the SD in full-length InsP(3)R, and an InsP(3)R in which its C-terminal transmembrane region was replaced by that from RyR1 was gated by InsP(3) and blocked by ryanodine. Activation mechanisms are conserved between InsP(3)R and RyR. Allosteric modulation of two similar domain interfaces within an N-terminal subunit reorients the first domain (SD or A domain), allowing it, through interactions of the second domain of an adjacent subunit (IBC-β or B domain), to gate the pore.     

Structural view of cadherin-mediated cell-cell adhesion

Following the multiplication of biochemical, biophysical and structural studies describing cadherin molecules and their interactions, several ideas have emerged to explain the mechanisms of cadherin-mediated cell adhesion. Although different models were proposed for cadherin interactions, a consensus has come forth considering lateral dimerization of cadherins as being a central component of the cell-cell adhesion process. This review summarizes the recent development in structural studies of cadherins. Received 14 September 1998; received after revision 14 November 1998; accepted 16 November 1998     

东莞市大气颗粒物中多环芳香烃的特征与来源研究

以PAHs的年度污染综合评价为基础,考察了东莞市虎门镇和松山湖地区大气颗粒物中PAHs浓度及季节变化特征;再利用文献报道的PAHs毒性指标,评价了健康影响的危害性;同时采用特定PAHs比值法,解析了东莞市大气颗粒中PAHs主要污染来源。     

热释电效应用于低温余热动力回收的研究

以热释电效应用于低温余热动力回收为背景,对采用40 μm厚的热释电材料共聚物偏氟乙烯-三氟乙烯(P(VDF-TrFE)(60/40))薄膜作工作介质的热释电转换循环进行了实验研究.实验结果表明:在避免失去自发极化的适宜工况条件下,可以直接实现连续的热释电转换循环;施加电压对热释电电流和热释电转换输出的电能密度都有较大的影响,在相同的温度范围和变化率下,随着施加电压的增加,热释电电流增大;提高低端电压和高低端压差有利于增加输出电能密度.在温度为40～70 ℃的范围内,当高端电压为900 V(电场强度为225 kV/cm)时,热释电转换净输出电能密度(单位体积热释电材料所生产的电能)可达40 mJ/cm3.这种热释电转换将在低温余热动力回收领域具有可能的应用前景.     

Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand

In a variety of cells, the Ca2+ signalling process is mediated by the endoplasmic-reticulum-membrane-associated Ca2+ release channel, inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R). Being ubiquitous and present in organisms ranging from humans to Caenorhabditis elegans, InsP3R has a vital role in the control of cellular and physiological processes as diverse as cell division, cell proliferation, apoptosis, fertilization, development, behaviour, memory and learning. Mouse type I InsP3R (InsP3R1), found in high abundance in cerebellar Purkinje cells, is a polypeptide with three major functionally distinct regions: the amino-terminal InsP3-binding region, the central modulatory region and the carboxy-terminal channel region. Here we present a 2.2-A crystal structure of the InsP3-binding core of mouse InsP3R1 in complex with InsP3. The asymmetric, boomerang-like structure consists of an N-terminal beta-trefoil domain and a C-terminal alpha-helical domain containing an 'armadillo repeat'-like fold. The cleft formed by the two domains exposes a cluster of arginine and lysine residues that coordinate the three phosphoryl groups of InsP3. Putative Ca2+-binding sites are identified in two separate locations within the InsP3-binding core.     

No high-mass protostars in the silhouette young stellar object M17-SO1

The birth of very massive stars is not well understood, in contrast to the formation process of low-mass stars like our Sun. It is not even clear that massive stars can form as single entities; rather, they might form through the mergers of smaller ones born in tight groups. The recent claim of the discovery of a massive protostar in M17 (a nearby giant ionized region) forming through the same mechanism as low-mass stars has therefore generated considerable interest. Here we show that this protostar has an intermediate mass of only 2.5 to 8 solar masses (M(o), contrary to the earlier claim of 20M(o) (ref. 8). The surrounding circumstellar envelope contains only 0.09M(o) and a much more extended local molecular cloud has 4-9M(o).     

An early extrasolar planetary system revealed by planetesimal belts in beta Pictoris

beta Pictoris (beta Pic) is a main-sequence star with an edge-on dust disk that might represent a state of the early Solar System. The dust does not seem to be a remnant from the original protoplanetary disk, but rather is thought to have been generated from large bodies like planetesimals and/or comets. The history and composition of the parent bodies can therefore be revealed by determining the spatial distribution, grain size, composition and crystallinity of the dust through high-resolution mid-infrared observations. Here we report that the sub-micrometre amorphous silicate grains around beta Pic have peaks in their distribution around 6, 16 and 30 au (1 au is the Sun-Earth distance), whereas the crystalline and micrometre-sized amorphous silicate grains are concentrated in the disk centre. As sub-micrometre grains are blown quickly out from the system by radiation pressure from the central star, the peaks indicate the locations of ongoing dust replenishment, which originates from ring-like distributions of planetesimals or 'planetesimal belts'.