Protein Deacetylase CobB Interplays with c-di-GMP
Protein Deacetylase CobB Interplays with c-di-GMP
Abstract As a ubiquitous bacterial secondary messenger, c-di-GMP plays key regulatory roles in processes such as bacterial motility and transcription regulation. CobB is the Sir2 family protein deacetylase that controls energy metabolism, chemotaxis and DNA supercoiling in many bacteria. Using an E.coli proteome microarray, we found that c-di-GMP strongly binds to CobB. Protein deacetylation assays showed that c-di-GMP inhibits CobB activity and thereby modulates the biogenesis of acetyl-CoA. Through mutagenesis studies, residues R8, R17 and E21 of CobB were shown to be required for c-di-GMP binding. Next, we found that CobB is an effective deacetylase of YdeH, a major diguanylate cyclase (DGC) of E.coli that is endogenously acetylated. Mass spectrometry analysis identified YdeH K4 as the major site of acetylation, and it could be deacetylated by CobB. Interestingly, deacetylation of YdeH enhances its stability and cyclase activity in c-di-GMP production. Thus, our work establishes a novel negative feedback loop linking c-di-GMP biogenesis and CobB-mediated protein deacetylation.
Tan Minjia、Xu Zhaowei、Hou Jingli、Zhang Hainan、Qian Lili、Czajkowsky Daniel M.、Guo Shujuan、Wang Shihua、Wu Fanlin、Li Haitao、Bi Lijun、Tao Sheng-ce、Feng Lei、Zhang Xingrun、Liu Chengxi、Jiang Hewei
The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong UniversityInstrumental Analysis Center, Shanghai Jiao Tong UniversityKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong UniversityThe Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesSchool of Biomedical Engineering, Shanghai Jiao Tong UniversityKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong UniversitySchool of Life Science, Fujian Agriculture and Forestry UniversityKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong UniversityMOE Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University||Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityNational Key Laboratory of Biomacromolecules, Key Laboratory of Non-Coding RNA and Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences||School of Stomatology and Medicine, Foshan UniversityKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University||State Key Laboratory of Oncogenes and Related Genes||School of Biomedical Engineering, Shanghai Jiao Tong UniversityInstrumental Analysis Center, Shanghai Jiao Tong UniversityMOE Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University||Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong UniversityKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University
分子生物学生物化学微生物学
c-di-GMPCobBdiguanylate cyclaseprotein acetylationnegative feedback loop
Tan Minjia,Xu Zhaowei,Hou Jingli,Zhang Hainan,Qian Lili,Czajkowsky Daniel M.,Guo Shujuan,Wang Shihua,Wu Fanlin,Li Haitao,Bi Lijun,Tao Sheng-ce,Feng Lei,Zhang Xingrun,Liu Chengxi,Jiang Hewei.Protein Deacetylase CobB Interplays with c-di-GMP[EB/OL].(2025-03-28)[2025-06-12].https://www.biorxiv.org/content/10.1101/362293.点此复制
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