The YdiU Domain Modulates Bacterial Stress Signaling through Mn2+-Dependent UMPylation
Yinlong Yang,
Yingying Yue,
Nannan Song,
Cuiling Li,
Zenglin Yuan,
Yan Wang,
Yue Ma,
Hui Li,
Fengyu Zhang,
Weiwei Wang,
Haihong Jia,
Peng Li,
Xiaobing Li,
Qi Wang,
Zhe Ding,
Hongjie Dong,
Lichuan Gu,
Bingqing Li
Affiliations
Yinlong Yang
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Yingying Yue
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Nannan Song
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Cuiling Li
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Zenglin Yuan
State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, China
Yan Wang
MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong 266003, China
Yue Ma
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Hui Li
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Fengyu Zhang
State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, China
Weiwei Wang
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Haihong Jia
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Peng Li
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Xiaobing Li
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Qi Wang
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China
Zhe Ding
Advanced Medical Research Institute, Translational Medicine Core Facility, Shandong University, Jinan, Shandong 250012, China
Hongjie Dong
State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, China
Lichuan Gu
State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, China
Bingqing Li
Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China; Corresponding author
Summary: Sensing stressful conditions and adjusting the cellular metabolism to adapt to the environment are essential activities for bacteria to survive in variable situations. Here, we describe a stress-related protein, YdiU, and characterize YdiU as an enzyme that catalyzes the covalent attachment of uridine-5′-monophosphate to a protein tyrosine/histidine residue, an unusual modification defined as UMPylation. Mn2+ serves as an essential co-factor for YdiU-mediated UMPylation. UTP and Mn2+ binding converts YdiU to an aggregate-prone state facilitating the recruitment of chaperones. The UMPylation of chaperones prevents them from binding co-factors or clients, thereby impairing their function. Consistent with the recent finding that YdiU acts as an AMPylator, we further demonstrate that the self-AMPylation of YdiU padlocks its chaperone-UMPylation activity. A detailed mechanism is proposed based on the crystal structures of Apo-YdiU and YdiU-AMPNPP-Mn2+ and on molecular dynamics simulation models of YdiU-UTP-Mn2+ and YdiU-UTP-peptide. In vivo data demonstrate that YdiU effectively protects Salmonella from stress-induced ATP depletion through UMPylation.
