This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6s5t
From Proteopedia
Legionella pneumophila SidJ-Human calmodulin complex
Structural highlights
FunctionSIDJ_LEGPH Glutamylase that mediates the covalent attachment of glutamate moieties to SdeA on one of the catalytic residues that is required for its mono-ADP-ribosyltransferase activity (PubMed:31330532, PubMed:31330531). In turn, inhibits SdeA ubiquitinating activity. Glutamylates also related SdeB, SdeC and SidE (PubMed:31330531, PubMed:31123136). Glutamylase activity only occurs in the host since it requires host calmodulin (PubMed:28497808, PubMed:31330532, PubMed:31330531, PubMed:31123136). May also reverse the SdeA-mediated substrate ubiquitination by cleaving the phosphodiester bond that links phosphoribosylated ubiquitin to protein substrates via its deubiquitinase activity (PubMed:28497808).[1] [2] [3] [4] Publication Abstract from PubMedThe family of bacterial SidE enzymes catalyses phosphoribosyl-linked (PR) serine ubiquitination and promotes infectivity of Legionella pneumophilia, a pathogenic bacterium causing Legionnaires' disease(1-3). SidEs share the genetic locus with the Legionella effector SidJ that spatiotemporally opposes their toxicity in yeast and mammalian cells, through an unknown mechanism(4-6). Deletion of SidJ leads to a significant defect in the growth of Legionella in both its natural host amoeba and in murine macrophages(4,5). Here, we demonstrate that SidJ is a glutamylase that modifies the catalytic glutamate in the mono-ADPribosyl transferase (mART) domain of SdeA thus blocking its ubiquitin (Ub) ligase activity. SidJ glutamylation activity requires interaction with calmodulin (CaM), a eukaryotic specific co-factor, and can be regulated by intracellular changes in Ca(2+) concentrations. The cryo-EM structure of SidJ/human apo-CaM complex revealed the architecture of this unique heterodimeric glutamylase. In infected cells, we show that SidJ mediates glutamylation of SidEs on the surface of Legionella-containing vacuoles (LCVs). Using quantitative proteomics, we also uncovered multiple host proteins as putative targets of SidJ-mediated glutamylation. Collectively, this study reveals the mechanism of SidE ligases inhibition by a SidJ/CaM glutamylase and opens new avenues for studying protein glutamylation, an understudied protein modification in higher eukaryotes. Inhibition of bacterial ubiquitin ligases by SidJ-calmodulin-catalysed glutamylation.,Bhogaraju S, Bonn F, Mukherjee R, Adams M, Pfleiderer MM, Galej WP, Matkovic V, Lopez-Mosqueda J, Kalayil S, Shin D, Dikic I Nature. 2019 Jul 22. pii: 10.1038/s41586-019-1440-8. doi:, 10.1038/s41586-019-1440-8. PMID:31330532[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
