最近一段时间，国内独立完成的研究结果频频登上Science，最新的两篇Science文章分别为清华大学施一公实验室和厦门大学韩家淮实验室完成。从以上两篇文章的署名单位来看，所有实验工作均完全由国内完成。
5月28日，Science在线发表了施一公实验室最新结构生物学研究成果，Structure and Mechanism of an Amino Acid Antiporter。文章的通讯作者是施一公教授，其他参与者工作单位都是清华大学。这是一篇施一公在中国的实验室发表的首篇Science文章。这篇文章主要研究大肠杆菌的肠道毒性，大肠杆菌O157的肠道致病性主要依赖于细菌内的耐酸性系统，依靠这一系统，大肠杆菌能在PH偏酸的胃中生存。在耐酸系统中，主要依靠一种精氨酸依赖性的反向转运体（antiporter）。施一公清华实验室主要研究大肠杆菌O157:H7的反向转运体AdiC的晶体结构。对AdiC的结构分析表明，AdiC结构保守，还获得了AdiC的配体结合残基结构。对分析耐酸系统中的反向转运体的功能机制具有重要的意义。
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Published Online May 28, 2009 |
Reports
Submitted on March 17, 2009
Accepted on April 30, 2009
Structure and Mechanism of an Amino Acid Antiporter
,,,
2 Center for Structural Biology, Department of Biological Sciences & Biotechnology, Tsinghua University, Beijing 100084, China.; School of Medicine, Tsinghua University, Beijing 100084, China.
* To whom correspondence should be addressed.
Yigong Shi , E-mail: shi-lab@tsinghua.edu.cn
These author contributed equally to this work.
Virulent enteric pathogens such as Escherichia coli strain O157:H7 rely on acid resistance (AR) systems to survive acidic environment in the stomach. A major component of AR is an arginine-dependent arginine:agmatine antiporter that expels intracellular protons. Here, we report the crystal structure of AdiC, the arginine:agmatine antiporter from E. coli O157:H7 and a member of the amino acid/polyamine/organocation (APC) superfamily of transporters at 3.6 Å resolution. The overall fold is similar to that of several Na+-coupled symporters. AdiC contains 12 transmembrane segments, forms a homodimer, and exists in an outward-facing, open conformation in the crystals. A conserved, acidic pocket opens to the periplasm. Structural and biochemical analysis reveals the essential ligand-binding residues, defines the transport route, and suggests a conserved mechanism for the antiporter activity.
6月4日，Science在线发表了韩家淮实验室关于细胞坏死的研究成果。细胞坏死（necrosis）是一个由肿瘤坏死因子TNF或其他细胞因子介导的死亡受体诱导的生物学过程，细胞坏死与细胞凋亡的启动机制一直不明。在本研究中，韩家淮教授实验室鉴定了一种RIP3蛋白，该蛋白是细胞凋亡与细胞坏死的生物开关。研究小组发现NIH3T3细胞中，蛋白激酶RIP3是启动细胞凋亡或是细胞坏死的重要分子开关，并且在其他细胞中，细胞坏死程序也需要有RIP3的参与。RIP3不会影响RIP1介导的细胞凋亡，但是却会影响RIP1介导的细胞坏死过程，RIP3能通过半胱天冬酶抑制剂zVAD增强细胞坏死作用。RIP3通过激活关键代谢酶的活性调节TNF介导的活性氧簇产量，活性氧簇能促进RIP3诱导细胞坏死。这些结果表明，细胞在受到死亡刺激后产生的应激能量代谢的调节对细胞选择自我凋亡和细胞坏死具有重要的意义。RIP3是调控细胞凋亡或是细胞坏死的生物学开关。
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Published Online June 4, 2009 |
Reports
Submitted on February 16, 2009
Accepted on May 21, 2009
RIP3, an Energy Metabolism Regulator that Switches TNF-Induced Cell Death from Apoptosis to Necrosis
2 The National Institute of Biological Sciences, Beijing, China.
* To whom correspondence should be addressed.
Jiahuai Han , E-mail: jhan@scripps.edu; jhan@xmu.edu.cn
Necrosis can be induced by stimulating death receptors with tumor necrosis factor (TNF) or other agonists; however, the underlying mechanism differentiating necrosis from apoptosis is largely unknown. We identified the protein kinase RIP3 as a molecular switch between TNF-induced apoptosis and necrosis in NIH3T3 cells, and found that RIP3 was required for necrosis in other cells. RIP3 did not affect RIP1-mediated apoptosis, but was required for RIP1-mediated necrosis and the enhancement of necrosis by the caspase inhibitor zVAD. By activating key enzymes of metabolic pathways, RIP3 regulated TNF-induced reactive oxygen species production, which partially accounts for RIP3’s ability to promote necrosis. Our data suggest that modulation of energy metabolism in response to death stimuli has an important role in the choice between apoptosis and necrosis.
标签：科学杂志
