梁毅

武漢大學生命科學學院教授

梁毅,男,漢族。博士,武漢大學生命科學學院生物化學與分子生物學教授、博士生導師。研究方向結構生物學-蛋白質結構與功能。

人物經歷


學習經歷

1985年7月畢業於武漢大學化學系,1998年6月在武漢大學獲得博士學位(導師:屈松生教授)。1998年7月至2000年12月在中國科學院生物物理研究所生物大分子國家重點實驗室從事蛋白質和分子酶學方面的博士後期研究工作(導師:鄒承魯院士)。

工作經歷

2001年1月至今作為武漢大學的引進人才,在武漢大學生命科學學院工作,2001年12月晉陞為教授,2002年7月評為博士生導師,2011年1月評選為985工程特聘教授。2004年入選教育部“新世紀優秀人才支持計劃”。2001-2002年在法國Louis Pasteur大學藥理學與物理化學國家重點實驗室(CNRS)做訪問教授(合作教授:Jacques Haiech教授)。2006-2007年在美國國立健康研究院(NIH)生物化學與遺傳學實驗室做訪問教授(合作教授:Allen P. Minton 教授) 。

研究方向


目前的主要研究領域和興趣
(1)體外和生理擁擠環境中蛋白質摺疊和錯誤摺疊機制;
(2)信號轉導網路中蛋白質相互作用機制;
(3)以蛋白質為靶標的藥物篩選和抗腫瘤的蛋白質新葯研發。
目前該實驗室主要從事朊病毒蛋白和Tau蛋白的翻譯后修飾、錯誤摺疊及其致病機制的研究。

主要貢獻


科研項目

1. 2013年蛋白質研究重大科學研究計劃資助課題:“翻譯后修飾對蛋白質功能的影響”(項目名稱:退行性疾病相關重要蛋白質翻譯后修飾的化學生物學研究),2013.01-2017.08,課題批准號:2013CB910702,課題負責人。
2.2006年蛋白質研究重大科學研究計劃資助課題:“蛋白質生成的質量控制”(項目名稱:蛋白質生成、摺疊、組裝和降解的規律及其質量控制),2006.08-2010.08,課題批准號:2006CB910301,課題負責人。
3.2012年蛋白質研究重大科學研究計劃資助課題:“蛋白質錯誤摺疊及分子伴侶的作用”(項目名稱:蛋白質的生成、修飾與質量控制),2012.01-2016.08,課題批准號:2012CB911003,課題組學術骨幹。
4.國家自然科學基金面上項目:“翻譯后修飾對人朊蛋白致病結構形成的調控”,2014.01-2017.12,項目批准號31370774,項目負責人。
5.國家自然科學基金面上項目:“鋅離子對人Tau蛋白致病結構形成的調控”,2012.01-2015.12,項目批准號31170744,項目負責人。
6.教育部“新世紀優秀人才支持計劃”資助項目:“G蛋白偶聯受體激酶與鈣調蛋白相互作用及調控機制的研究”,2005.01-2007.12,項目批准號NCET-04-0670,項目負責人。
7.國家自然科學基金重大研究計劃《真核生物重要生命活動的信息基礎》資助項目:“鈣調蛋白與靶蛋白相互作用及調控機制的信息基礎”,2005.01-2007.12,項目批准號90408012,項目負責人。
8.國家高技術研究發展計劃(863計劃)資助課題:微流控晶元篩選G蛋白受體疾病藥物的應用研究,2004.10-2005.06,項目批准號2004AA404260,子課題負責人。
9.國家自然科學基金面上項目:“模擬生理環境中朊蛋白錯誤摺疊與聚集的機制”,2010.01-2012.12,項目批准號30970599,項目負責人。
10.國家自然科學基金面上項目:“大分子擁擠環境中溶菌酶錯誤摺疊與聚集的機制”,2008.01-2010.12,項目批准號30770421,項目負責人。
11. 國家自然科學基金面上項目:“大分子擁擠環境中蛋白質相互作用的機制”,2004.01-2006.12,項目批准號30370309,項目負責人。
12.國家自然科學基金面上項目:“銠(III)多吡啶配合物與RNA 的作用機理”,2006.01-2008.12,項目批准號30570421,本室主持。
13.國家自然科學基金面上項目:“單抗探針探測蛋白質摺疊機制的微量熱研究”,2000.01-2002.12,項目批准號39970164,項目負責人。
14.武漢大學人才引進啟動基金資助項目:分子伴侶幫助蛋白質摺疊機制的微量熱學研究,2001.01-2005.12,項目批准號00029,項目負責人。

代表性論文

1. Xiao-Ling Liu, Ji-Ying Hu, Meng-Yun Hu, Yi Zhang, Zheng-Yuan Hong, Xiao-Qing Cheng, Jie Chen, Dai-Wen Pang,YiLiang(2015). Sequence-dependent abnormal aggregation of human Tau fragment in an inducible cell model.BBA - Molecular Basis of Disease1852, 1561-1573.
2.Hai-Li Zhu, Cristina Fernández, Jun-Bao Fan, Frank Shewmaker, Jie Chen, Allen P. Minton,YiLiang(2010). Quantitative characterization of heparin binding to Tau protein: Implication for inducer mediated Tau filament formation.J. Biol. Chem.285, 3592-3599.
3.Zhong-Ying Mo, Ying-Zhu Zhu, Hai-Li Zhu, Jun-Bao Fan, Jie Chen,YiLiang(2009). Low micromolar zinc accelerates the fibrillization of human Tau via bridging Cys-291 and Cys-322.J. Biol. Chem.284, 34648-34657.
4.Zheng Zhou, Jun-Bao Fan, Hai-Li Zhu, Frank Shewmaker, Xu Yan, Xi Chen, Jie Chen, Geng-Fu Xiao, Lin Guo,Yi Liang(2009). Crowded cell-like environment accelerates the nucleation step of amyloidogenic protein misfolding.J. Biol. Chem.284, 30148-30158.
5.Bing-Rui Zhou,Yi Liang, Fen Du, Zheng Zhou, Jie Chen (2004). Mixed macromolecular crowding accelerates the oxidative refolding of reduced, denatured lysozyme: Implications for protein folding in intracellular environments.J. Biol. Chem.279, 55109-55116.
6.Yi Liang, Fen Du, Sarah Sanglier, Bing-Rui Zhou, Yi Xia, Alain Van Dorsselaer, Clarisse Maechling, Marie-Claude Kilhoffer, Jacques Haiech (2003). Unfolding of rabbit muscle creatine kinase induced by acid. A study using electrospray ionization mass spectrometry, isothermal titration calorimetry, and fluorescence spectroscopy.J. Biol. Chem.278, 30098-30105.
7.Zheng Zhou, Xu Yan, Kai Pan, Jie Chen, Zheng-Sheng Xie, Geng-Fu Xiao, Fu-Quan Yang,YiLiang(2011). Fibril formation of the rabbit/human/bovine prion proteins.Biophys. J.101, 1483-1492.
8.Ming Jiao, Hong-Tao Li, Jie Chen, Allen P. Minton,YiLiang(2010). Attractive protein-polymer interactions markedly alter the effect of macromolecular crowding on protein association equilibria.Biophys. J.99, 914-923.
9.Fen Du, Zheng Zhou, Zhong-Ying Mo, Jun-Zhi Shi, Jie Chen,Yi Liang(2006). Mixed macromolecular crowding accelerates the refolding of rabbit muscle creatine kinase: Implications for protein folding in physiological environments.J. Mol. Biol.364, 469-482.
10.Fang Yang (Jr.), Min Zhang, Bing-Rui Zhou, Jie Chen,Yi Liang(2006). Oleic acid inhibits amyloid formation of the intermediate of alpha-lactalbumin at moderately acidic pH.J. Mol. Biol.362, 821-834.
11.Yu Chen, Ceyang Su, Min Ke, Xu Jin, Li-Rong Xu, Zhou Zhang, Andong Wu, Ying Sun, Zhouning Yang, Po Tien, Tero Ahola,Yi Liang, Xinqi Liu, Deyin Guo (2011). Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 29-O-methylation by nsp16/nsp10 protein complex.PLoS Pathog.7, e1002294.
12.Lei Wang, Sheng-Jian Li, Ateesh Sidhu, Li Zhu,Yi Liang, Robert B. Freedman, Chih-chen Wang (2009). Reconstitution of human Ero1-La/protein-disulfide isomerase oxidative folding pathway in vitro.J. Biol. Chem.284, 199-206.
13.Xu Yan, Jun-Jie Huang, Zheng Zhou, Jie Chen,YiLiang(2014). How does domain replacement affect fibril formation of the rabbit/human prion proteins.PLoS One9, e113238.
14.Li-Rong Xu, Xiao-Ling Liu, Jie Chen,YiLiang(2013). Protein disulfide isomerase interacts with Tau protein and inhibits its fibrillization.PLoS One8, e76657.
15.Cheng Li, Wen-Chang Xu, Zhen-Sheng Xie, Kai Pan, Jiao Hu, Jie Chen, Dai-Wen Pang, Fu-Quan Yang,YiLiang(2013). Cupric ions induce the oxidation and trigger the aggregation of human superoxide dismutase 1.PLoS One8, e65287.
16.Sheng-Rong Meng, Ying-Zhu Zhu, Tong Guo, Xiao-Ling Liu, Jie Chen,YiLiang(2012). Fibril-Forming motifs are essential and sufficient for the fibrillization of human Tau.PLoS One7, e38903.
17.Qian Ma, Jun-Bao Fan, Zheng Zhou, Bing-Rui Zhou, Sheng-Rong Meng, Ji-Ying Hu, Jie Chen,YiLiang(2012). The contrasting effect of macromolecular crowding on amyloid fibril formation.PLoS One7, e36288.
18.Hai-Li Zhu, Sheng-Rong Meng, Jun-Bao Fan, Jie Chen,YiLiang(2011). Fibrillization of human Tau is accelerated by exposure to lead via interaction with His-330 and His-362.PLoS One6, e25020.
19.Ling-Jia Wu, Li-Rong Xu, Jun-Ming Liao, Jie Chen,YiLiang(2011). Both the C-terminal polylysine region and the farnesylation of K-RasB are important for its specific interaction with calmodulin.PLoS One6, e21929.
20.Yu-Ling Zhou, Jun-Ming Liao, Jie Chen,Yi Liang(2006). Macromolecular crowding enhances the binding of superoxide dismutase to xanthine oxidase: Implications for protein-protein interactions in intracellular environments.Int. J. Biochem. Cell Biol.38, 1986-1994.
21.Hong Xu,Yi Liang, Peng Zhang, Fen Du, Bing-Rui Zhou, Jun Wu, Jian-Hong Liu, Zhi-Gang Liu, Liang-Nian Ji (2005). Biophysical studies of a ruthenium(II) polypyridyl complex binding to DNA and RNA prove that nucleic acid structure has significant effects on binding behaviors.J. Biol. Inorg. Chem.10, 529-538.
22.Jun Wu, Fen Du, Peng Zhang, Izhar Ahmed Khan, Jie Chen,Yi Liang(2005). Thermodynamics of the interaction of aluminum ions with DNA: Implications for the biological function of aluminum.J. Inorg. Biochem.99, 1145-1154.
23.Zheng Zhou, Jun-Ming Liao, Peng Zhang, Jun-Bao Fan, Jie Chen,Yi Liang(2011). Parkinson disease drug screening based on the interaction between D2 dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis.Protein Cell2, 899-905.
24.Fan-Lou Kong, Wei Cheng, Jie Chen,YiLiang(2011). D-ribose glycates beta2-microglobulin to form aggregates with high cytotoxicity through a ROS-mediated pathway.Chem.-Biol. Interact.194, 69-78.
25.Min Zhang, Fang Yang (Jr.), Fang Yang, Jie Chen, Cong-Yi Zheng,YiLiang(2009). Cytotoxic aggregates of alpha-lactalbumin induced by unsaturated fatty acid induce apoptosis in tumor cells.Chem.-Biol. Interact.180, 131-142.
26.Fang Yang, Bing-Rui Zhou, Peng Zhang, Yan-Feng Zhao, Jie Chen,Yi Liang(2007). Binding of ferulic acid to cytochrome c enhances stability of the protein at physiological pH and inhibits cytochrome c-induced apoptosis.Chem.-Biol. Interact.170, 231-243.
27.Jun-Bao Fan, Jie Chen,Yi Liang (2008). Oxidative refolding of reduced, denatured lysozyme in AOT reverse micelles.J. Colloid Interface Sci.322, 95-103.
28.Kai Pan, Chuan-Wei Yi, Jie Chen,Yi Liang(2015). Zinc significantly changes the aggregation pathway and the conformation of aggregates of human prion protein.Biochim. Biophys. Acta1854, 907-918.
29.Jun-Ming Liao, Zhong-Ying Mo, Ling-Jia Wu, Jie Chen,Yi Liang(2008). Binding of calcium ions to Ras promotes Ras guanine nucleotide exchange under emulated physiological conditions.Biochim. Biophys. Acta1784, 1560-1569.
30.Bing-Rui Zhou, Zheng Zhou, Qing-Lian Hu, Jie Chen,Yi Liang(2008). Mixed macromolecular crowding inhibits amyloid formation of hen egg white lysozyme.Biochim. Biophys. Acta1784, 472-480.
31.Fang Yang (Jr.), Min Zhang, Jie Chen,Yi Liang(2006). Structural changes of alpha-lactalbumin induced by low pH and oleic acid.Biochim. Biophys. Acta1764, 1389-1396.
32.Nan Chen, Jun-Bao Fan, Jin Xiang, Jie Chen,Yi Liang(2006). Enzymatic hydrolysis of microcrystalline cellulose in reverse micelles.Biochim. Biophys. Acta1764, 1029-1035.