Crystal structures of the kinase domain of PpkA, a key regulatory component of T6SS, reveal a general inhibitory mechanism
文献类型：期刊论文
| 作者 | Li, PP; Xu, DQ; Ma, TQ; Wang, DY; Li, WD; He, JH; Ran, TT; Wang, WW |
| 刊名 | BIOCHEMICAL JOURNAL
 |
| 出版日期 | 2018 |
| 卷号 | 475期号:-页码:2209-2224 |
| 关键词 | VI SECRETION SYSTEM DEPENDENT PROTEIN-KINASE GRAM-NEGATIVE BACTERIA MYCOBACTERIUM-TUBERCULOSIS SERINE/THREONINE KINASE CATALYTIC DOMAIN CONFORMATIONAL PLASTICITY PSEUDOMONAS-AERUGINOSA ACTIVATION MECHANISM EDWARDSIELLA-TARDA |
| ISSN号 | 0264-6021 |
| DOI | 10.1042/BCJ20180077 |
| 文献子类 | 期刊论文 |
| 英文摘要 | The type VI secretion system (T6SS) is a versatile and widespread export system found in many Gram-negative bacteria that delivers effector proteins into target cells. The functions of T6SSs are tightly regulated by diverse mechanisms at multiple levels, including post-translational modification through threonine phosphorylation via the Ser/Thr protein kinase (STPK) PpkA. Here, we identified that PpkA is essential for T6SS secretion in Serratia marcescens since its deletion eliminated the secretion of haemolysin co-regulated protein, while the periplasmic and transmembrane portion of PpkA was found to be disposable for T6SS secretion. We further determined the crystal structure of the kinase domain of PpkA (PpkA-294). The structure of PpkA-294 was determined in its apo form to a 1.6 angstrom resolution as well as in complex with ATP to a 1.41 angstrom resolution and with an ATP analogue AMP-PCP to a 1.45 angstrom resolution. The residues in the activation loop of PpkA-294 were fully determined, and the N-terminus of the loop was folded into an unprecedented inhibitory helix, revealing that the PpkA kinase domain was in an auto-inhibitory state. The ternary MgATP-PpkA-294 complex was also inactive with nucleotide ribose and phosphates in unexpected and unproductive conformations. The aC-helix in the inactive PpkA-294 adopted a conformation towards the active site but with the conserved glutamate in the helix rotated away, which we suggest to be a general conformation for all STPK kinases in the inactive form. Structural comparison of PpkA with its eukaryotic homologues reinforced the universal regulation mechanism of protein kinases. |
| 语种 | 英语 |
| 源URL | [http://ir.sinap.ac.cn/handle/331007/30895]  |
| 专题 | 上海应用物理研究所_中科院上海应用物理研究所2011-2017年 |
| 作者单位 | 1.Nanjing Agr Univ, Coll Life Sci, Dept Microbiol, Nanjing 210095, Jiangsu, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai 201204, Peoples R China 3.Jiangsu Acad Agr Sci, Inst Agr Prod Proc, Nanjing 210014, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, PP,Xu, DQ,Ma, TQ,et al. Crystal structures of the kinase domain of PpkA, a key regulatory component of T6SS, reveal a general inhibitory mechanism[J]. BIOCHEMICAL JOURNAL,2018,475(-):2209-2224. |
| APA | Li, PP.,Xu, DQ.,Ma, TQ.,Wang, DY.,Li, WD.,...&Wang, WW.(2018).Crystal structures of the kinase domain of PpkA, a key regulatory component of T6SS, reveal a general inhibitory mechanism.BIOCHEMICAL JOURNAL,475(-),2209-2224. |
| MLA | Li, PP,et al."Crystal structures of the kinase domain of PpkA, a key regulatory component of T6SS, reveal a general inhibitory mechanism".BIOCHEMICAL JOURNAL 475.-(2018):2209-2224. |
入库方式： OAI收割
来源：上海应用物理研究所
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