6lna | pdb_00006lna
YdiU complex with AMPNPP and Mn2+
Structural highlights
FunctionSELO_ECOLI Catalyzes the transfer of adenosine 5'-monophosphate (AMP) to Ser, Thr and Tyr residues of target proteins (AMPylation). Cannot use GTP, CTP or UTP as cosubstrate. AMPylates SucA at 'Thr-405' and GrxA on 'Tyr-13'. Regulates protein S-glutathionylation levels probably by AMPylation of deglutathionylation enzymes such as GrxA. Probably involved in redox homeostasis.[1] Publication Abstract from PubMedSensing 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. Mn(2+) serves as an essential co-factor for YdiU-mediated UMPylation. UTP and Mn(2+) 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-Mn(2+) and on molecular dynamics simulation models of YdiU-UTP-Mn(2+) and YdiU-UTP-peptide. In vivo data demonstrate that YdiU effectively protects Salmonella from stress-induced ATP depletion through UMPylation. The YdiU Domain Modulates Bacterial Stress Signaling through Mn(2+)-Dependent UMPylation.,Yang Y, Yue Y, Song N, Li C, Yuan Z, Wang Y, Ma Y, Li H, Zhang F, Wang W, Jia H, Li P, Li X, Wang Q, Ding Z, Dong H, Gu L, Li B Cell Rep. 2020 Sep 22;32(12):108161. doi: 10.1016/j.celrep.2020.108161. PMID:32966796[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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