cAMP-regulated Protein Lysine Acetylases in Mycobacteria
cAMP-regulated Protein Lysine Acetylases in Mycobacteria
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DOI：
10.1074/jbc.m110.118398
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发表时间：
2010-08-06
影响因子：
4.8
通讯作者：
Visweswariah, Sandhya S.
中科院分区：
文献类型：
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作者：
Nambi, Subhalaxmi;Basu, Nirmalya;Visweswariah, Sandhya S.
由结核分枝杆菌合成的环状AMP已被证明在发病机制中发挥作用。然而，在致病性和非致病性分枝杆菌中发现的高水平的细胞内cAMP表明，在这些生物体中，cAMP还调节着其他重要的生物过程。我们在此描述了耻垢分枝杆菌和结核分枝杆菌（分别为MSMEG_5458和Rv0998）中新的camp结合蛋白的生化特性，它们包含一个环核苷酸结合结构域，融合到一个与乙酰转移酶GNAT家族相似的结构域。我们在分枝杆菌中检测了蛋白质赖氨酸乙酰化，并鉴定了一个通用应激蛋白（USP）作为MSMEG_5458的底物。USP中赖氨酸残基的乙酰化是由cAMP调控的，使用MSMEG_5458删除的菌株，我们表明USP确实是MSMEG_5458的体内底物。Rv0998蛋白显示出严格的cAMP依赖性乙酰化USP，尽管其对cAMP的亲和力低于MSMEG_5458。因此，该报告不仅首次证明了分枝杆菌中蛋白质赖氨酸乙酰化，而且还描述了环核苷酸结合域和蛋白质乙酰转移酶之间独特的功能相互作用。
Cyclic AMP synthesized by Mycobacterium tuberculosis has been shown to play a role in pathogenesis. However, the high levels of intracellular cAMP found in both pathogenic and nonpathogenic mycobacteria suggest that additional and important biological processes are regulated by cAMP in these organisms. We describe here the biochemical characterization of novel cAMP-binding proteins in M. smegmatis and M. tuberculosis (MSMEG_5458 and Rv0998, respectively) that contain a cyclic nucleotide binding domain fused to a domain that shows similarity to the GNAT family of acetyltransferases. We detect protein lysine acetylation in mycobacteria and identify a universal stress protein (USP) as a substrate of MSMEG_5458. Acetylation of a lysine residue in USP is regulated by cAMP, and using a strain deleted for MSMEG_5458, we show that USP is indeed an in vivo substrate for MSMEG_5458. The Rv0998 protein shows a strict cAMP-dependent acetylation of USP, despite a lower affinity for cAMP than MSMEG_5458. Thus, this report not only represents the first demonstration of protein lysine acetylation in mycobacteria but also describes a unique functional interplay between a cyclic nucleotide binding domain and a protein acetyltransferase.