No abstract

Bacterial pathogens have evolved effector proteins with ubiquitin E3 ligase activities through structural mimicking. Here we report the crystal structure of the Shigella flexneri type III effector IpaH3, a member of the leucine-rich repeat (LRR)-containing bacterial E3 family. The LRR domain is structurally similar to Yersinia pestis YopM and potentially binds to substrates. The structure of the C-terminal E3 domain differs from the typical RING- and HECT-type E3s. IpaH3 synthesizes a Lys48-linked ubiquitin chain, and the reaction requires noncovalent binding between ubiquitin and a specific E2, UbcH5. Free ubiquitin serves as an acceptor for IpaH3-catalyzed ubiquitin transfer. Cys363 within a conserved CXD motif acts as a nucleophile to catalyze ubiquitin transfer through a transthiolation reaction. The D365N mutant is devoid of E3 activities but turns into a potent ubiquitin-E2 thioesterase. Our analysis establishes a structurally and mechanistically distinct class of ubiquitin ligases found exclusively in pathogenic or symbiotic bacteria.

Some types of circular RNA (circRNA) are aberrantly expressed in human diseases including hepatocellular carcinoma (HCC). However, its regulation mechanism and diagnostic roles are largely unknown. Here, we identified that circRNA_104075 (circ_104075) was highly expressed in HCC tissues, cell lines and serum. Mechanistically, HNF4a bound to the −1409 to −1401 region of the circ_104075 promoter to stimulate the expression of circ_104075. Moreover, circ_104075 acted as a ceRNA to upregulate YAP expression by absorbing miR-582-3p. Interestingly, an N6-methyladenosine (m6A) motif was identified in the 353–357 region of YAP 3′UTR, and this m6A modification was essential for the interaction between miR-582-3p and YAP 3′UTR. Further, the diagnostic performance of circ_104075 was evaluated. The area under the receiver operating characteristic (AUC-ROC) for circ_104075 was 0.973 with a sensitivity of 96.0% and a specificity of 98.3%. Collectively, we determined that circ_104075 was highly expressed in HCC and elucidated its upstream and downstream regulatory mechanisms. circ_104075 additionally has the potential to serve as a new diagnostic biomarker in HCC. Targeting circ_104075 may provide new strategies in HCC diagnosis and therapy.

Tensile-strained Mxene/carbon nanotube (CNT) porous microspheres were developed as an electrocatalyst for the lithium polysulfide (LiPS) redoxr eaction. The internal stress on the surface results in lattice distortion with expanding TiÀTi bonds,e ndowing the Mxene nanosheet with abundant active sites and regulating the d-band center of Ti atoms upshifted closer to the Fermi level, leading to strengthened LiPS adsorbability and accelerated catalytic conversion. The macroporous framework offers uniformed sulfur distribution, potent sulfur immobilization, and large surface area. The composite interwoven by CNT tentacle enhances conductivity and prevents the restacking of Mxene sheets.This combination of tensile strain effect and hierarchical architecture design results in smooth and favorable trapping-diffusion-conversion of LiPS on the interface.T he Li-S battery exhibits an initial capacity of 1451 mAh g À1 at 0.2 C, rate capability up to 8C,and prolonged cycle life.