PT  - JOURNAL ARTICLE
AU  - Yinlong Yang
AU  - Yingying Yue
AU  - Cuiling Li
AU  - Nannan Song
AU  - Zenglin Yuan
AU  - Yan Wang
AU  - Yue Ma
AU  - Hui Li
AU  - Fengyu Zhang
AU  - Weiwei Wang
AU  - Haihong Jia
AU  - Peng Li
AU  - Xiaobing Li
AU  - Hongjie Dong
AU  - Lichuan Gu
AU  - Bingqing Li
TI  - The YdiU Domain Modulates Bacterial Stress Signaling through UMPylation
AID  - 10.1101/692707
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 692707
4099  - http://biorxiv.org/content/early/2019/07/04/692707.short
4100  - http://biorxiv.org/content/early/2019/07/04/692707.full
AB  - Sensing stressful conditions and adjusting metabolism to adapt to the environment is essential for bacteria to survive in changeable situations. Here, we discover a new stress-induced protein YdiU, demonstrate a role of YdiU in bacterial heat stress resistance and identify YdiU as an enzyme that catalyzes the covalent attachment of uridine 5’-monophosphate to a tyrosine or histidine residue of bacterial proteins—a novel modification defined as UMPylation. Consistent with the recent finding that YdiU acts as an AMPylator, we further reveal that self-AMPylation of YdiU negatively regulates its UMPylation activity. The detailed molecular mechanism of YdiU-mediated UMPylation and substrate selectivity are proposed based on the determination of the crystal structures of Apo-YdiU, YdiU-ATP and YdiU-AMP complexes and a molecular dynamics simulation model of the YdiU-UTP complex. Biochemical data show that UMPylation of chaperones mediated by YdiU prevents them from binding either downstream co-factors or their substrates, thereby impairing their function. Interestingly, UMPylation mediated by YdiU also promotes the degradation of chaperones. In vivo data show that YdiU effectively protects Salmonella from heat injury by preventing stress-induced ATP depletion and UMPylation occurs in response to heat stress in a YdiU-dependent manner. Together, our results illuminate new biological functions of the YdiU domain family, highlight the importance of UMPylation in bacterial signal transduction, and reveal a potential mechanism by which bacteria adapt to different levels of stressful environment.