The YdiU Domain Modulates Bacterial Stress Signaling through UMPylation

Yinlong Yang, Yingying Yue, Cuiling Li, Nannan Song, Zenglin Yuan, Yan Wang, Yue Ma, Hui Li, Fengyu Zhang, Weiwei Wang, Haihong Jia, Peng Li, Xiaobing Li, Hongjie Dong, Lichuan Gu and Bingqing Li

Jul 24, 2019

Received Date: 4th July 19

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.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature