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.
Original language | English (US) |
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Pages (from-to) | 4527-4539.e8 |
Journal | Molecular cell |
Volume | 81 |
Issue number | 21 |
DOIs | |
State | Published - Nov 4 2021 |
Keywords
- Legionella
- SdeA
- SdeB
- SdeC
- SdjA
- SidE
- SidJ
- effectors
- glutamylation
- pseudokinase
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology