4lzp

Structure of the TIR domain of the immunosuppressor BtpA from Brucella

spinqualitylabelsall models 4lzp, resolution 3.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4lzp is a 4 chain structure with sequence from Brucella melitensis ATCC 23457. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.15Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BTPA_BRUMB Virulence factor that interferes with host Toll-like receptor 2 (TLR2) and TLR4 signaling, resulting in the reduction of dendritic cell maturation, inhibition of pro-inflammatory cytokine secretion and impaired NF-kappa-B activation in macrophages (PubMed:18266466). Acts as a NAD(+) hydrolase (NADase) by catalyzing cleavage of NAD(+) into ADP-D-ribose (ADPR) and nicotinamide (PubMed:29395922). In addition to ADPR, also generates a cyclization variant of cyclic ADPR (cADPR), termed v-cADPR, for which the cyclizing bond is unknown (PubMed:29395922). Publication Abstract from PubMed BtpA/Btp1/TcpB is a virulence factor produced by Brucella species that possesses a Toll interleukin-1 receptor (TIR) domain. Once delivered into the host cell, BtpA interacts with MyD88 to interfere with TLR signalling and modulates microtubule dynamics. Here the crystal structure of the BtpA TIR domain at 3.15A is presented. The structure shows a dimeric arrangement of a canonical TIR domain, similar to the Paracoccus denitrificans Tir protein but secured by a unique long N-terminal alpha-tail that packs against the TIR:TIR dimer. Structure-based mutations and multi-angle light scattering experiments characterized the BtpA dimer conformation in solution. The structure of BtpA will help with studies to understand the mechanisms involved in its interactions with MyD88 and with microtubules. Structure of the Toll/interleukin 1 receptor (TIR) domain of the immunosuppressive Brucella effector BtpA/Btp1/TcpB.,Kaplan-Turkoz B, Koelblen T, Felix C, Candusso MP, O'Callaghan D, Vergunst AC, Terradot L FEBS Lett. 2013 Nov 1;587(21):3412-6. doi: 10.1016/j.febslet.2013.09.007. Epub, 2013 Sep 25. PMID:24076024 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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