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Structure and mechanism of human diacylglycerol O-acyltransferase 1 期刊论文
NATURE, 2020, 581 (7808) : 329-+
作者:  Wu, Fan;  Zhao, Su;  Yu, Bin;  Chen, Yan-Mei;  Wang, Wen;  Song, Zhi-Gang;  Hu, Yi;  Tao, Zhao-Wu;  Tian, Jun-Hua;  Pei, Yuan-Yuan;  Yuan, Ming-Li;  Zhang, Yu-Ling;  Dai, Fa-Hui;  Liu, Yi;  Wang, Qi-Min;  Zheng, Jiao-Jiao;  Xu, Lin;  Holmes, Edward C.;  Zhang, Yong-Zhen
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

The structure of human diacylglycerol O-acyltransferase 1, a membrane protein that synthesizes triacylglycerides, is solved with cryo-electron microscopy, providing insight into its function and mechanism of enzymatic activity.


Diacylglycerol O-acyltransferase 1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans(1). DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylation of lipids and proteins(2,3). How human DGAT1 and other mammalian members of the MBOAT family recognize their substrates and catalyse their reactions is unknown. The absence of three-dimensional structures also hampers rational targeting of DGAT1 for therapeutic purposes. Here we present the cryo-electron microscopy structure of human DGAT1 in complex with an oleoyl-CoA substrate. Each DGAT1 protomer has nine transmembrane helices, eight of which form a conserved structural fold that we name the MBOAT fold. The MBOAT fold in DGAT1 forms a hollow chamber in the membrane that encloses highly conserved catalytic residues. The chamber has separate entrances for each of the two substrates, fatty acyl-CoA and diacylglycerol. DGAT1 can exist as either a homodimer or a homotetramer and the two forms have similar enzymatic activity. The N terminus of DGAT1 interacts with the neighbouring protomer and these interactions are required for enzymatic activity.


  
The online competition between pro- and anti-vaccination views 期刊论文
NATURE, 2020, 582 (7811) : 230-+
作者:  Wu, Fan;  Zhao, Su;  Yu, Bin;  Chen, Yan-Mei;  Wang, Wen;  Song, Zhi-Gang;  Hu, Yi;  Tao, Zhao-Wu;  Tian, Jun-Hua;  Pei, Yuan-Yuan;  Yuan, Ming-Li;  Zhang, Yu-Ling;  Dai, Fa-Hui;  Liu, Yi;  Wang, Qi-Min;  Zheng, Jiao-Jiao;  Xu, Lin;  Holmes, Edward C.;  Zhang, Yong-Zhen
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

Insights into the interactions between pro- and anti-vaccination clusters on Facebook can enable policies and approaches that attempt to interrupt the shift to anti-vaccination views and persuade undecided individuals to adopt a pro-vaccination stance.


Distrust in scientific expertise(1-14) is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks(2-4), as happened for measles in 2019(5,6). Homemade remedies(7,8) and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice(9-11). There is a lack of understanding about how this distrust evolves at the system level(13,14). Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change(11), and highlight the key role of network cluster dynamics in multi-species ecologies(15).


  
Origin of complexity in haemoglobin evolution 期刊论文
NATURE, 2020
作者:  Cheema, Suraj S.;  Kwon, Daewoong;  Shanker, Nirmaan;  dos Reis, Roberto;  Hsu, Shang-Lin;  Xiao, Jun;  Zhang, Haigang;  Wagner, Ryan;  Datar, Adhiraj;  McCarter, Margaret R.;  Serrao, Claudy R.;  Yadav, Ajay K.;  Karbasian, Golnaz;  Hsu, Cheng-Hsiang;  Tan, Ava J.;  Wang, Li-Chen;  Thakare, Vishal;  Zhang, Xiang;  Mehta, Apurva;  Karapetrova, Evguenia;  Chopdekar, Rajesh, V;  Shafer, Padraic;  Arenholz, Elke;  Hu, Chenming;  Proksch, Roger;  Ramesh, Ramamoorthy;  Ciston, Jim;  Salahuddin, Sayeef
收藏  |  浏览/下载:50/0  |  提交时间:2020/07/03

Most proteins associate into multimeric complexes with specific architectures(1,2), which often have functional properties such as cooperative ligand binding or allosteric regulation(3). No detailed knowledge is available about how any multimer and its functions arose during evolution. Here we use ancestral protein reconstruction and biophysical assays to elucidate the origins of vertebrate haemoglobin, a heterotetramer of paralogous alpha- and beta-subunits that mediates respiratory oxygen transport and exchange by cooperatively binding oxygen with moderate affinity. We show that modern haemoglobin evolved from an ancient monomer and characterize the historical '  missing link'  through which the modern tetramer evolved-a noncooperative homodimer with high oxygen affinity that existed before the gene duplication that generated distinct alpha- and beta-subunits. Reintroducing just two post-duplication historical substitutions into the ancestral protein is sufficient to cause strong tetramerization by creating favourable contacts with more ancient residues on the opposing subunit. These surface substitutions markedly reduce oxygen affinity and even confer cooperativity, because an ancient linkage between the oxygen binding site and the multimerization interface was already an intrinsic feature of the protein'  s structure. Our findings establish that evolution can produce new complex molecular structures and functions via simple genetic mechanisms that recruit existing biophysical features into higher-level architectures.


Experimental analysis of reconstructed ancestral globins reveals that haemoglobin'  s complex tetrameric structure and oxygen-binding functions evolved by simple genetic and biophysical mechanisms.


  
Metabolic regulation of gene expression by histone lactylation 期刊论文
NATURE, 2019, 574 (7779) : 575-+
作者:  Zhang, Di;  Tang, Zhanyun;  Huang, He;  Zhou, Guolin;  Cui, Chang;  Weng, Yejing;  Liu, Wenchao;  Kim, Sunjoo;  Lee, Sangkyu;  Perez-Neut, Mathew;  Ding, Jun;  Czyz, Daniel;  Hu, Rong;  Ye, Zhen;  He, Maomao;  Zheng, Y. George;  Shuman, Howard A.;  Dai, Lunzhi;  Ren, Bing;  Roeder, Robert G.;  Becker, Lev;  Zhao, Yingming
收藏  |  浏览/下载:28/0  |  提交时间:2019/11/27
Super-elastic ferroelectric single-crystal membrane with continuous electric dipole rotation 期刊论文
SCIENCE, 2019, 366 (6464) : 475-+
作者:  Dong, Guohua;  Li, Suzhi;  Yao, Mouteng;  Zhou, Ziyao;  Zhang, Yong-Qiang;  Han, Xu;  Luo, Zhenlin;  Yao, Junxiang;  Peng, Bin;  Hu, Zhongqiang;  Huang, Houbing;  Jia, Tingting;  Li, Jiangyu;  Ren, Wei;  Ye, Zuo-Guang;  Ding, Xiangdong;  Sun, Jun;  Nan, Ce-Wen;  Chen, Long-Qing;  Li, Ju;  Liu, Ming
收藏  |  浏览/下载:9/0  |  提交时间:2019/11/27
Atomically dispersed Fe3+ sites catalyze efficient CO2 electroreduction to CO 期刊论文
SCIENCE, 2019, 364 (6445) : 1091-+
作者:  Gu, Jun;  Hsu, Chia-Shuo;  Bai, Lichen;  Chen, Hao Ming;  Hu, Xile
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/27
Convergent regulatory evolution and loss of flight in paleognathous birds 期刊论文
SCIENCE, 2019, 364 (6435) : 74-+
作者:  Sackton, Timothy B.;  Grayson, Phil;  Cloutier, Alison;  Hu, Zhirui;  Liu, Jun S.;  Wheeler, Nicole E.;  Gardner, Paul P.;  Clarke, Julia A.;  Baker, Allan J.;  Clamp, Michele;  Edwards, Scott V.
收藏  |  浏览/下载:90/0  |  提交时间:2019/11/27
Single-cell multiomics sequencing and analyses of human colorectal cancer 期刊论文
SCIENCE, 2018, 362 (6418) : 1060-+
作者:  Bian, Shuhui;  Hou, Yu;  Zhou, Xin;  Li, Xianlong;  Yong, Jun;  Wang, Yicheng;  Wang, Wendong;  Yan, Jia;  Hu, Boqiang;  Guo, Hongshan;  Wang, Jilian;  Gao, Shuai;  Mao, Yunuo;  Dong, Ji;  Zhu, Ping;  Xiu, Dianrong;  Yan, Liying;  Wen, Lu;  Qiao, Jie;  Tang, Fuchou;  Fu, Wei
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27
The paraventricular thalamus is a critical thalamic area for wakefulness 期刊论文
SCIENCE, 2018, 362 (6413) : 429-+
作者:  Ren, Shuancheng;  Wang, Yaling;  Yue, Faguo;  Cheng, Xiaofang;  Dang, Ruozhi;  Qiao, Qicheng;  Sun, Xueqi;  Li, Xin;  Jiang, Qian;  Yao, Jiwei;  Qin, Han;  Wang, Guanzhong;  Liao, Xiang;  Gao, Dong;  Xia, Jianxia;  Zhang, Jun;  Hu, Bo;  Yan, Junan;  Wang, Yanjiang;  Xu, Min;  Han, Yunyun;  Tang, Xiangdong;  Chen, Xiaowei;  He, Chao;  Hu, Zhian
收藏  |  浏览/下载:9/0  |  提交时间:2019/11/27
VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma 期刊论文
SCIENCE, 2018, 361 (6399) : 290-295
作者:  Zhang, Jing;  Wu, Tao;  Simon, Jeremy;  Takada, Mamoru;  Saito, Ryoichi;  Fan, Cheng;  Liu, Xian-De;  Jonasch, Eric;  Xie, Ling;  Chen, Xian;  Yao, Xiaosai;  Teh, Bin Tean;  Tan, Patrick;  Zheng, Xingnan;  Li, Mingjie;  Lawrence, Cortney;  Fan, Jie;  Geng, Jiang;  Liu, Xijuan;  Hu, Lianxin;  Wang, Jun;  Liao, Chengheng;  Hong, Kai;  Zurlo, Giada;  Parker, Joel S.;  Auman, J. Todd;  Perou, Charles M.;  Rathmell, W. Kimryn;  Kim, William Y.;  Kirschner, Marc W.;  Kaelin, William G., Jr.;  Baldwin, Albert S.;  Zhang, Qing
收藏  |  浏览/下载:11/0  |  提交时间:2019/11/27