4PUF

Complex between the Salmonella T3SS effector SlrP and its human target thioredoxin-1

Summary for 4PUF

• Entry DOI: 10.2210/pdb4puf/pdb
• Descriptor: E3 ubiquitin-protein ligase SlrP, Thioredoxin (2 entities in total)
• Functional Keywords: lrr domain, nel domain, e3 ubiquitin ligase, human thioredoxin 1, ligase -oxidoreductase complex, ligase-oxidoreductase complex, ligase/oxidoreductase
• Biological source: Salmonella enterica subsp. enterica serovar Typhimurium; More
• Cellular location: Secreted: D0ZRB2; Nucleus: P10599
• Total number of polymer chains: 4
• Total formula weight: 172247.14

Authors

Zouhir, S.,Bernal-Bayard, J.,Cordero-Alba, M.,Cardenal-Munoz, E.,Guimaraes, B.,Lazar, N.,Ramos-Morales, F.,Nessler, S. (deposition date: 2014-03-13, release date: 2014-09-17, Last modification date: 2024-02-28)

Primary citation

Zouhir, S.,Bernal-Bayard, J.,Cordero-Alba, M.,Cardenal-Munoz, E.,Guimaraes, B.,Lazar, N.,Ramos-Morales, F.,Nessler, S.
The structure of the Slrp-Trx1 complex sheds light on the autoinhibition mechanism of the type III secretion system effectors of the NEL family.
Biochem.J., 464:135-144, 2014

PubMed Abstract: Salmonella infections are a leading cause of bacterial foodborne illness in the U.S.A. and the European Union Antimicrobial therapy is often administered to treat the infection, but increasingly isolates are being detected that demonstrate resistance to multiple antibiotics. Salmonella enterica contains two virulence-related T3SS (type III secretion systems): one promotes invasion of the intestine and the other one mediates systemic disease. Both of them secrete the SlrP protein acting as E3 ubiquitin ligase in human host cells where it targets Trx1 (thioredoxin-1). SlrP belongs to the NEL family of bacterial E3 ubiquitin ligases that have been observed in two distinct autoinhibitory conformations. We solved the 3D structure of the SlrP-Trx1 complex and determined the Trx1 ubiquitination site. The description of the substrate-binding mode sheds light on the first step of the activation mechanism of SlrP. Comparison with the available structural data of other NEL effectors allowed us to gain new insights into their autoinhibitory mechanism. We propose a molecular mechanism for the regulation of SlrP in which structural constraints sequestrating the NEL domain would be sequentially released. This work thus constitutes a new milestone in the understanding of how these T3SS effectors influence pathogen virulence. It also provides the fundamental basis for future development of new antimicrobials.

PubMed: 25184225
DOI: 10.1042/BJ20140587

Experimental method

X-RAY DIFFRACTION (3.296 Å)