期刊
MOLECULAR CELL
卷 81, 期 21, 页码 4527-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2021.08.007
关键词
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资金
- NIH [DP2GM137419, F30HL143859, U24GM129547]
- W.M. Keck Foundation grant
- Welch Foundation grant [I-1911]
- Polish National Agency for Scientific Exchange scholarship [PPN/BEK/2018/1/00431]
- Cancer Prevention & Research Institute of Texas (CPRIT) [RP170644]
- Office of Biological and Environmental Research
- CPRIT [RR150033]
Studies reveal that Legionella effectors SidJ and its homolog SdjA adopt a kinase fold to regulate the activity of SidE ligases through glutamylation reaction, uncovering the structural and mechanistic basis in which the kinase fold catalyzes non-ribosomal amino acid ligations.
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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