6IAI

StoD is a novel Salmonella Typhi type III secretion system E3 ubiquitin ligase effector

6IAI の概要

• エントリーDOI: 10.2210/pdb6iai/pdb
• 分子名称: Protein of uncharacterized function (DUF1076) (2 entities in total)
• 機能のキーワード: salmonella t3ss effector ubiquitin ligase, protein binding
• 由来する生物種: Salmonella typhi
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 55586.07

構造登録者

McDowell, M.A.,Lea, S.M. (登録日: 2018-11-26, 公開日: 2019-05-29, 最終更新日: 2024-05-15)

主引用文献

McDowell, M.A.,Byrne, A.M.,Mylona, E.,Johnson, R.,Sagfors, A.,Crepin, V.F.,Lea, S.,Frankel, G.
The S . Typhi effector StoD is an E3/E4 ubiquitin ligase which binds K48- and K63-linked diubiquitin.
Life Sci Alliance, 2:-, 2019

PubMed Abstract: (e.g., serovars Typhi and Typhimurium) relies on translocation of effectors via type III secretion systems (T3SS). Specialization of typhoidal serovars is thought to be mediated via pseudogenesis. Here, we show that the Typhi STY1076/t1865 protein, named StoD, a homologue of the enteropathogenic /enterohemorrhagic NleG, is a T3SS effector. The StoD C terminus (StoD-C) is a U-box E3 ubiquitin ligase, capable of autoubiquitination in the presence of multiple E2s. The crystal structure of the StoD N terminus (StoD-N) at 2.5 Å resolution revealed a ubiquitin-like fold. In HeLa cells expressing StoD, ubiquitin is redistributed into puncta that colocalize with StoD. Binding assays showed that StoD-N and StoD-C bind the same exposed surface of the β-sheet of ubiquitin, suggesting that StoD could simultaneously interact with two ubiquitin molecules. Consistently, StoD interacted with both K63- (K = 5.6 ± 1 μM) and K48-linked diubiquitin (K = 15 ± 4 μM). Accordingly, we report the first Typhi-specific T3SS effector. We suggest that StoD recognizes and ubiquitinates pre-ubiquitinated targets, thus subverting intracellular signaling by functioning as an E4 enzyme.

PubMed: 31142637
DOI: 10.26508/lsa.201800272

実験手法

X-RAY DIFFRACTION (2.54 Å)