Structure of the human CLC-7/Ostm1 complex reveals a novel state

CLC-7 functions as a Cl?/H+ exchanger in lysosomes. Defects in CLC-7 and its β-subunit, Ostm1, result in osteopetrosis and neurodegeneration. Here, we present the cryogenic electron microscopy (cryo-EM) structure of the human CLC-7/Ostm1 complex (HsCLC-7/Ostm1) at a resolution of 3.6 ?. Our structure reveals a new state of the CLC-7/Ostm1 heterotetramer, in which the cytoplasmic domain of CLC-7 is absent, likely due to high flexibility. The disordered cytoplasmic domain is probably not able to restrain CLC-7 subunits and thus allow their relative movements. The movements result in an approximately half smaller interface between the CLC-7 transmembrane domains than that in a previously reported CLC-7/Ostm1 structure with a well-folded cytoplasmic domain. Key interactions involving multiple osteopetrosis-related residues are affected by the interface change.     

基于遗传算法的船舶分段运输调度方法

为解决船厂平板运输车搬运船舶分段的日程计划问题,建立了利用最少数量的平板运输车完成分段搬运作业,以及所有分段搬运作业完成时间最小化的两阶段优化模型,提出了基于遗传算法的2种启发式方法以实现模型求解,并用数值实验的方法进行验证.结果表明,所提出的2种方法都能够较好地完成船舶分段运输调度计划,并实现平板运输车的高效利用.     

pHi regulatory ion transporters: an update on structure, regulation and cell function

Intracellular pH (pH_i) is a major regulator of various and critical cellular functions. A close regulation of pH_i is thus mandatory to maintain normal cellular activity. To this end, all cells express ion transporters that carry across their plasma membrane H⁺ or equivalent H⁺ into and out of the cell. Besides pH_i, these ion transporters are under the regulation of neurohormonal stimuli. This review summarises the molecular identity, regulation and function of the main membrane pH-regulatory ion transporters. Received 30 December 1998; received after revision 4 February 1999; accepted 9 February 1999     

用可编程控制器实现的重型平台运输车转向控制系统

根据 1 30t升降平台运输车对转向系统的特殊要求 ,通过分析转向驱动机构的传动特性 ,采用C2 0 0HG可编程控制器为核心设计了该车的转向控制系统 ,编制了控制软件 在以PID为基础的控制算法中结合车轮的不同位置和偏转方向进行计算修正 ,达到了车轮在所处的任意位置向左或向右偏转时 ,转向系统的工作速度特性都基本保持一致 从而使转向过程中各车轮组之间的偏转关系始终满足车辆转向特性要求 ,实现转向控制系统的准确、稳定和快速灵敏     

Effect on membrane transport in the erythrocytes by band 3 cross-linking

Band 3 and glucose transport protein (GluT1) are two kinds of important proteins in the human erythrocyte membranes. Bis(sulfosuccinimidyl)suberate (BS³), an impermeable cross-linker of band 3, inhibited NO₂ ⁻ transport, showing that anion exchange is affected by the association state of band 3 in the intact erythrocyte membranes. At the same time, the rates of glucose transport of both exit and entry declined. The amount of monomers of band 3 was decreased after treatment of the erythrocytes with BS³, but there was no change in GluT1 according to the SDS-PAGE patterns. This demonstrates that band 3 and GluT1 would be linkaged together in the erythrocyte membranes for the requirement of rapid and cooperative performance of physiological functions of the membrane proteins.     

Iron metabolism in the mononuclear phagocyte system

The maintenance of body iron homeostasis requires the coordination of multiple regulatory mechanisms of iron metabolism. The mononuclear phagocyte system （MPS, composed of monocytes, macrophages, and their precursor cells） is crucial in the maintenance of iron homeostasis. Recycling of iron is carried out by specialized macrophages via engulfment of aged erythrocytes. The iron stores of macrophages depend on the levels of recovered and exported iron. However, the molecular mechanisms underlying iron homeostasis in macrophages are poorly understood. Recent studies characterizing the function and regulation of natural resistance-associated mac- rophage protein 1 （Nrampl）, divalent metal transporter 1 （DMT1）, HLA-linked hemechromatosis gene （HFE）, ferroportin 1 （FPN1）, and hepcidin are rapidly expanding our knowledge on the molecular level of MPS iron handling. These studies are deepening our under- standing about the molecular mechanism of iron homeostasis and iron-related diseases.     

Nucleotide binding domains of human CFTR: a structural classification of critical residues and disease-causing mutations.

Defective function of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) causes CF, the most frequent lethal inherited disease among the Caucasian population. The structure of this chloride ion channel includes two nucleotide-binding domains (NBDs), whose ATPase activity controls channel gating. Recently, the experimental structures of mouse and human CFTR NBD1 and our model of the human CFTR NBD1/NBD2 heterodimer have provided new insights into specific structural features of the CFTR NBD dimer. In the present work, we provide a structural classification of CF-causing mutations which may complement the existing functional classification. Our analysis also identified amino acid residues which may play a critical role in interdomain interaction and are located at the NBD1-NBD2 interface or on the surface of the dimer. In particular, a cluster of aromatic amino acids, which includes F508 and straddles the two NBDs, might be directly involved in the interaction of the NBD1/NBD2 heterodimer with the channel-forming membrane-spanning domains.Received 24 May 2005; received after revision 13 June 2005; accepted 18 June 2005     

钠离子依赖的中性氨基酸转运蛋白SNAT2-HA融合蛋白的构建及鉴定

钠离子依赖的中性氨基酸转运蛋白SNAT2在哺乳动物组织中广泛表达,具有转运中性氨基酸的功能,在谷氨酸-谷氨酰胺循环、肝脏糖质新生等生物通路中发挥重要作用．为了方便测定SNAT2在细胞膜上的表达和定位,本研究采用PCR扩增和酶切连接将HA标签蛋白与SNAT2的C末端连接,构建了真核生物表达载体pBK-CMVA（1098—1300）-SNAT2-HA表达载体．用脂质体转染法将该表达载体瞬时转染到HEK293T细胞中,通过Westernblot法检测到SNAT2-HA融合蛋白在细胞膜上的正确表达和定位．pBK-CMV△（1098-1300）-SNAT2-HA表达载体的成功构建,为今后对SNAT2的结构和功能的研究提供了有效方法．     

煤矸石发电厂气力除灰控制系统分析研究

简要介绍了某煤矸石发电厂1号炉、2号炉气力正压密相气力输灰系统及其操作,论述了布袋除尘器飞灰输送逻辑描述、除灰步序,详细分析了DCS控制系统在电厂除灰控制系统中的应用特点。