| Structural highlights
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). [THIO_HUMAN] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity.[1] [2] [3] [4] [5] ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).[6] [7] [8] [9] [10]
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[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jacquot JP, de Lamotte F, Fontecave M, Schurmann P, Decottignies P, Miginiac-Maslow M, Wollman E. Human thioredoxin reactivity-structure/function relationship. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1375-81. PMID:2176490
- ↑ Hirota K, Matsui M, Iwata S, Nishiyama A, Mori K, Yodoi J. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-8. PMID:9108029
- ↑ Wei SJ, Botero A, Hirota K, Bradbury CM, Markovina S, Laszlo A, Spitz DR, Goswami PC, Yodoi J, Gius D. Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation. Cancer Res. 2000 Dec 1;60(23):6688-95. PMID:11118054
- ↑ Mitchell DA, Marletta MA. Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine. Nat Chem Biol. 2005 Aug;1(3):154-8. Epub 2005 Jul 10. PMID:16408020 doi:http://dx.doi.org/nchembio720
- ↑ Mitchell DA, Morton SU, Fernhoff NB, Marletta MA. Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11609-14. Epub 2007 Jul 2. PMID:17606900 doi:http://dx.doi.org/0704898104
- ↑ Jacquot JP, de Lamotte F, Fontecave M, Schurmann P, Decottignies P, Miginiac-Maslow M, Wollman E. Human thioredoxin reactivity-structure/function relationship. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1375-81. PMID:2176490
- ↑ Hirota K, Matsui M, Iwata S, Nishiyama A, Mori K, Yodoi J. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-8. PMID:9108029
- ↑ Wei SJ, Botero A, Hirota K, Bradbury CM, Markovina S, Laszlo A, Spitz DR, Goswami PC, Yodoi J, Gius D. Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation. Cancer Res. 2000 Dec 1;60(23):6688-95. PMID:11118054
- ↑ Mitchell DA, Marletta MA. Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine. Nat Chem Biol. 2005 Aug;1(3):154-8. Epub 2005 Jul 10. PMID:16408020 doi:http://dx.doi.org/nchembio720
- ↑ Mitchell DA, Morton SU, Fernhoff NB, Marletta MA. Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11609-14. Epub 2007 Jul 2. PMID:17606900 doi:http://dx.doi.org/0704898104
- ↑ 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. 2014 Nov 15;464(1):135-44. doi: 10.1042/BJ20140587. PMID:25184225 doi:http://dx.doi.org/10.1042/BJ20140587
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