4jmf
Crystal structure of ExoT (residues 28 -77)- SpcS complex from Pseudomonas aeruginosa at 2.1 angstromCrystal structure of ExoT (residues 28 -77)- SpcS complex from Pseudomonas aeruginosa at 2.1 angstrom
Structural highlights
FunctionEXOT_PSEAE Bifunctional effector protein that is secreted and delivered by the type III secretion system into eukaryotic target cells. The N-terminus encodes a GTPase-activating protein activity, whereas the C-terminus encodes an ADP-ribosyltransferase activity (PubMed:11298647). ADP-ribosylates several eukaryotic proteins including CT10 regulator of kinase (Crk) proteins (PubMed:12807879). In turn, induces atypical anoikis apoptosis by transforming Crk adaptor protein into a cytotoxin (PubMed:26020630). Affects host cell morphology by disrupting the actin cytoskeleton (PubMed:14688136). In addition to this activity, acts via its N-terminal region as a GTPase-activating protein (GAP) for host Rho GTPases including RhoA, Rac1, Cdc42 and Ras (PubMed:11895987). The GAP domain activity induces mitochondrial disruption in the target host cell by activating host caspases 3 and 9 that execute cellular death (PubMed:26451042). This activity also causes stress fiber disassembly (PubMed:11895987).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedExoT belongs to the family of type 3 secretion system (T3SS) effector toxins in Pseudomonas aeruginosa, known to be one of the major virulence determinant toxins that cause chronic and acute infections in immuno-compromised individuals, burn victims and cystic fibrosis patients. Here, we report the X-ray crystal structure of the amino terminal fragment of effector toxin ExoT, in complex with full-length homodimeric chaperone SpcS at 2.1 A resolution. The full-length dimeric chaperone SpcS has the conserved alpha-beta-beta-beta-alpha-beta-beta-alpha fold of class I chaperones, the characteristic hydrophobic patches for binding effector proteins and a conserved polar cavity at the dimeric interface. The stable crystallized amino terminal fragment of ExoT consists of a chaperone binding domain and a membrane localization domain that wraps around the dimeric chaperone. Site-directed mutagenesis experiments and a molecular dynamics study complement each other in revealing Asn65, Phe67 and Trp88 as critical dimeric interfacial residues that can strongly influence the effector-chaperone interactions. DATABASE: The atomic coordinates and structure factors of ExoT-SpcS complex (code 4JMF) have been deposited in the Protein Data Bank Japan (PDBj), Institute for Protein Research, Osaka University. Interfacial residues of SpcS chaperone affects binding of effector toxin ExoT in Pseudomonas aeruginosa: novel insights from structural and computational studies.,Dey S, Datta S FEBS J. 2014 Jan 4. doi: 10.1111/febs.12704. PMID:24387107[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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