AI Article Synopsis
- The Legionella effector SidJ, resembling a kinase, catalyzes a unique reaction involving glutamylation, instead of transferring phosphate from ATP like typical kinases.
- Cryo-EM reconstructions reveal the mechanism by which SidJ adenylates a specific Glu in SidE, forming a stable reaction intermediate crucial for its activity.
- The study also identifies SdjA, a paralog of SidJ, as a glutamylase that plays a role in regulating SidE ubiquitin ligases during Legionella infection, highlighting a new aspect of SidE family regulation.
Article Abstract
The kinase domain transfers phosphate from ATP to substrates. However, the Legionella effector SidJ adopts a kinase fold, yet catalyzes calmodulin (CaM)-dependent glutamylation to inactivate the SidE ubiquitin ligases. The structural and mechanistic basis in which the kinase domain catalyzes protein glutamylation is unknown. Here we present cryo-EM reconstructions of SidJ:CaM:SidE reaction intermediate complexes. We show that the kinase-like active site of SidJ adenylates an active-site Glu in SidE, resulting in the formation of a stable reaction intermediate complex. An insertion in the catalytic loop of the kinase domain positions the donor Glu near the acyl-adenylate for peptide bond formation. Our structural analysis led us to discover that the SidJ paralog SdjA is a glutamylase that differentially regulates the SidE ligases during Legionella infection. Our results uncover the structural and mechanistic basis in which the kinase fold catalyzes non-ribosomal amino acid ligations and reveal an unappreciated level of SidE-family regulation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571041 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2021.08.007 | DOI Listing |
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