Structural insight into the recognition of the linear ubiquitin assembly complex by Shigella E3 ligase IpaH1.4/2.5.

Pathogenic bacteria deliver virulence factors called effectors into host cells in order to facilitate infection. The Shigella effector proteins IpaH1.4 and IpaH2.

The HOIL-1L ligase modulates immune signalling and cell death via monoubiquitination of LUBAC.

The linear ubiquitin chain assembly complex (LUBAC), which consists of HOIP, SHARPIN and HOIL-1L, promotes NF-κB activation and protects against cell death by generating linear ubiquitin chains. LUBAC contains two RING-IBR-RING (RBR) ubiquitin ligases (E3), and the HOIP RBR is responsible for catalysing linear ubiquitination. We found that HOIL-1L RBR plays a crucial role in regulating LUBAC.

Bacterial effectors and their functions in the ubiquitin-proteasome system: insight from the modes of substrate recognition.

Protein ubiquitination plays indispensable roles in the regulation of cell homeostasis and pathogenesis of neoplastic, infectious, and neurodegenerative diseases. Given the importance of this modification, it is to be expected that several pathogenic bacteria have developed the ability to utilize the host ubiquitin system for their own benefit. Modulation of the host ubiquitin system by bacterial effector proteins inhibits innate immune responses and hijacks central signaling pathways.

Structural basis for the recognition of Ubc13 by the Shigella flexneri effector OspI.

Ubc13 is a ubiquitin-conjugating enzyme that plays a key role in the nuclear factor-κB signal transduction pathway in human diseases. The Shigella flexneri effector OspI affects inflammatory responses by catalyzing the deamidation of a specific glutamine residue at position 100 in Ubc13 during infection. This modification prevents the activation of the TNF (tumor necrosis factor) receptor-associated factor 6, leading to modulation of the diacylglycerol-CBM (CARD-Bcl10-Malt1) complex-TNF receptor-associated factor 6-nuclear factor-κB signaling pathway.

New crystal structure of the proteasome-dedicated chaperone Rpn14 at 1.6 Å resolution.

The 26S proteasome is an ATP-dependent protease responsible for selective degradation of polyubiquitylated proteins. Recent studies have suggested that proteasome assembly is a highly ordered multi-step process assisted by specific chaperones. Rpn14, an assembly chaperone for ATPase-ring formation, specifically recognizes the ATPase subunit Rpt6.