4puf | pdb_00004puf

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

spinqualitylabelsall models 4puf, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4puf is a 4 chain structure with sequence from Homo sapiens and Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SLRP_SALT1 Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway. Can ubiquitinate both ubiquitin and host TXN (Thioredoxin). Leads to significant decrease of thioredoxin activity and increase of host cell death (By similarity). Publication Abstract from PubMed 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. The structure of the Slrp-Trx1 complex sheds light on the autoinhibition mechanism of the type III secretion system effectors of the NEL family.,Zouhir S, Bernal-Bayard J, Cordero-Alba M, Cardenal-Munoz E, Guimaraes B, Lazar N, Ramos-Morales F, Nessler S Biochem J. 2014 Nov 15;464(1):135-44. doi: 10.1042/BJ20140587. PMID:25184225 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thioredoxin 3D structures Ubiquitin protein ligase 3D structures

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