+検索条件
-Structure paper
タイトル | Structural and mechanistic basis for protein glutamylation by the kinase fold. |
---|---|
ジャーナル・号・ページ | Mol Cell, Vol. 81, Issue 21, Page 4527-44539.e8, Year 2021 |
掲載日 | 2021年11月4日 |
著者 | Adam Osinski / Miles H Black / Krzysztof Pawłowski / Zhe Chen / Yang Li / Vincent S Tagliabracci / |
PubMed 要旨 | 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 ...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. |
リンク | Mol Cell / PubMed:34407442 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.5 - 2.8 Å |
構造データ | EMDB-23862, PDB-7mir: EMDB-23863, PDB-7mis: |
化合物 | ChemComp-AMP: ChemComp-MG: ChemComp-ATP: ChemComp-CA: ChemComp-NA: |
由来 |
|
キーワード | TRANSFERASE / HYDROLASE/LIGASE / SidJ / SdeA / CaM / complex / Intermediate / Acyl / Adenylate / Legionella / Ubiquitination / HYDROLASE-LIGASE complex / TRANSFERASE/LIGASE / SdeC / TRANSFERASE-LIGASE complex |