结核分枝杆菌中的泛素样蛋白-蛋白酶体系统研究进展

摘要/Abstract

摘要： 结核分枝杆菌（Mycobacterium tuberculosis, Mtb）是引起结核病这一严重威胁全球人类健康的灾难性传染病的病原体。它具有很强的生存能力，可在巨噬细胞中以一种潜伏的状态长期存在；并且其细胞壁厚，抗菌药物难以透过，加之其生长缓慢，抗结核治疗不当易使其产生耐药菌株。近年来由耐药Mtb引起的耐多药结核病（multidrug-resistant TB，MDR-TB）、广泛耐药结核病（extensively drug-resistant TB，XDR-TB），以及全耐药结核病（totally drug-resistant TB，TDR-TB）的出现，加之Mtb与艾滋病病毒双重感染疫情的上升，使得全球结核病防治工作当前面临的形势依然十分严峻。与普通的结核病的治疗相比，对这些类型的耐药结核病的治疗更加昂贵和困难，并且其治疗失败率和死亡率也明显增加。因此，寻找新的更有效的抗结核药物作用靶点对于结核病尤其是耐药结核病的治疗已刻不容缓。

关键词: 蛋白酶体, 结核分枝杆菌, 结核病, 真核生物, 研究进展, 泛素连接酶, 蛋白质, 抗结核治疗, 底物, 原核生物

刘翠华黄红娜王琪郑焙文宝利. 结核分枝杆菌中的泛素样蛋白-蛋白酶体系统研究进展[J]. 中国防痨杂志, 2011, 33(7): 445-448.

Liu Cuihua, Huang Hongna, Wang Qi, Zheng Peiwen, Bao Li. [J]. Chinese Journal of Antituberculosis, 2011, 33(7): 445-448.

参考文献

［1］World Health Organization. Anti-tuberculosis drug resistance in the world: fourth global report［R］. World Health Organization report 2008. WHO/HTM/TB/2008: 394.

［2］Migliori GB, De Iaco G, Besozzi G, Centis R, Cirillo DM. First tuberculosis cases in Italy resistant to all tested drugs［J］. Euro Surveill, 2007, 12 (5):E070517.1.

［3］中国防痨协会. 耐药结核病化学治疗指南(2009)［J］. 中国防痨杂志,2010, 32 (4): 181-198.

［4］Cheng Y, Pieters J. Novel proteasome inhibitors as potential drugs to combat tuberculosis［J］. J Mol Cell Biol, 2010, 2 (4): 173-175.

［5］Goldberg AL. Protein degradation and protection against misfolded or damaged proteins［J］. Nature, 2003, 426 (6968): 895-899. 

［6］赵天锁, 任贺, 郝继辉. 泛素蛋白酶体通路的研究进展［J］. 山东医药, 2009, 49 (32): 113-114.

［7］陈建华, 汤正好. 泛素-蛋白酶体系统与免疫系统的关系［J］. 国际免疫学杂志, 2010, 33 (4): 286-289.

［8］Darwin KH. Prokaryotic ubiquitinlike protein (Pup)，proteasomes and pathogenesis［J］. Nat Rev Microbiol, 2009, 7 (7): 485-491.

［9］Burns KE, Liu WT, Boshoff HI, Dorrestein PC, Barry CE 3rd. Proteasomal protein degradation in Mycobacteria is dependent upon a prokaryotic ubiquitin-like protein［J］. J Biol Chem, 2009, 284 (5): 3069-3075.

［10］Kraut DA, Matouschek A. Pup grows up: in vitro characterization of the degradation of pupylated proteins［J］. EMBO J, 2010, 29 (7): 1163-1164. 

［11］Festa RA, McAllister F, Pearce MJ, Mintseris J, Burns KE, Gygi SP, Darwin KH. Prokayrotic ubiquitin-like protein (Pup) proteome of Mycobacterium tuberculosis［corrected］［J］. PLoS One, 2010, 5 (1): e8589. 

［12］Cerda-Maira F, Darwin KH. The Mycobacterium tuberculosis proteasome:more than just a barrel-shaped protease［J］. Microbes Infect, 2009, 11 (14/15): 1150-1155.

［13］Sutter M, Striebel F, Damberger FF, Allain FH, Weber-Ban E. A distinct structural region of the prokaryotic ubiquitin-like protein (Pup) is recognized by the N-terminal domain of the proteasomal ATPase Mpa［J］. FEBS Lett, 2009, 583 (19): 3151-3157. 

［14］Liao S, Shang Q, Zhang X, Zhang J, Xu C, Tu X. Pup, a prokaryotic ubiquitin-like protein, is an intrinsically disordered protein［J］. Biochem J, 2009, 422(2): 207-215. 

［15］Burns KE, Pearce MJ, Darwin KH. Prokaryotic ubiquitin-like protein provides a two-part degron to Mycobacterium proteasome substrates［J］. J Bacteriol, 2010, 192 (11): 2933-2935. 

［16］Lin G, Tsu C, Dick L, Zhou XK, Nathan C. Distinct specificities of Mycobacterium tuberculosis and mammalian proteasomes for N-acetyl tripeptide substrates［J］. J Biol Chem, 2008, 283 (49): 34423-34431.

［17］Hu G, Lin G, Wang M, Dick L, Xu RM, Nathan C, Li H. Structure of the Mycobacterium tuberculosis proteasome and mechanism of inhibition by a peptidyl boronate［J］. Mol Microbiol, 2006, 59 (5): 1417-1428.

［18］Li D, Li H, Wang T, Pan H, Lin G, Li H. Structural basis for the assembly and gate closure mechanisms of the Mycobacterium tuberculosis 20S proteasome［J］. EMBO J, 2010, 29 (12): 2037-2047. 

［19］Mukherjee S, Orth K.Micrabiology. A protein pupylation paradigm［J］. Science, 2008, 322 (5904): 1062-1063.

［20］Pearce MJ, Mintseris J, Ferreyra J,Gygi SP,Darwin KM. Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis［J］.Science,2008,322 (14):1104-1107.

［21］Striebel F, Imkamp F, Sutter M, Steiner M, Mamedov A, Weber-Ban E. Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes［J］. Nat Struct Mol Biol, 2009, 16 (6): 647-651. 

［22］Cerda-Maira FA, Pearce MJ, Fuortes M, Bishai WR, Hubbard SR, Darwin KH. Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis［J］. Mol Microbiol, 2010, 77 (5): 1123-1135. 

［23］Pearce MJ, Arora P, Festa RA, Butler-Wu SM, Gokhale RS,Darwin KH. Identification of substrates of the Mycobacterium tuberculosis proteasome［J］. EMBO J, 2006, 25 (22): 5423-5432. 

［24］Imkamp F, Rosenberger T, Striebel F, Keller PM, Amstutz B, Sander P, Weber-Ban E. Deletion of dop in Mycobacterium smegmatis abolishes pupylation of protein substrates in vivo［J］. Mol Microbiol, 2010, 75 (3): 744-754. 

［25］Wang T, Li H, Lin G, Tang C, Li D, Nathan C, Darwin KH, Li H. Structural insights on the Mycobacterium tuberculosis proteasomal ATPase Mpa［J］. Structure, 2009, 17 (10): 1377-1385. 

［26］Salgame P. PUPylation provides the punch as Mycobacterium tuberculosis battles the host macrophage［J］. Cell Host Microbe, 2008, 4 (5): 415-416. 

［27］Pieters J, Ploegh H.Microbiology. Chemical warfare and mycobacterial defense［J］. Science, 2003, 302 (5652): 1900-1902.

［28］Gandotra S, Schnappinger D, Monteleone M, Hillen W, Ehrt S. In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice［J］. Nat Med, 2007, 13 (12): 1515-1520.

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