6nkl

2.2 A resolution structure of VapBC-1 from nontypeable Haemophilus influenzae

spinqualitylabelsall models 6nkl, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6nkl is a 4 chain structure with sequence from "bacterium_influenzae"_lehmann_and_neumann_1896 "bacterium influenzae" lehmann and neumann 1896. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: vapC1, vapC, BV136_01367, BVZ80_01200, CH628_04345, NCTC11872_02278 ("Bacterium influenzae" Lehmann and Neumann 1896), vapB1, BV136_01366, BVZ80_01199, CH628_04350 ("Bacterium influenzae" Lehmann and Neumann 1896) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [A0A2R3FUY7_HAEIF] Toxic component of a toxin-antitoxin (TA) system. An RNase.[HAMAP-Rule:MF_00265] Publication Abstract from PubMed Toxin-antitoxin (TA) gene pairs have been identified in nearly all bacterial genomes sequenced to date and are thought to facilitate persistence and antibiotic tolerance. TA loci are classified into various types based upon the characteristics of their antitoxins, with those in type II expressing proteic antitoxins. Many toxins from type II modules are ribonucleases that maintain a PilT N-terminus (PIN) domain containing conserved amino acids considered essential for activity. The vapBC (virulence associated protein) TA system is the largest subfamily in this class, and has been linked to pathogenesis of nontypeable Haemophilus influenzae (NTHi). In this study, the crystal structure of the VapBC-1 complex from NTHi was determined to 2.20 A resolution. Based on this structure, aspartate-to-asparagine and glutamate-to-glutamine mutations of four conserved residues in the PIN domain of the VapC-1 toxin were constructed and the effects of the mutations on protein-protein interactions, growth of Escherichia coli and pathogenesis ex vivo were tested. Finally, a novel model system was designed and utilized that consists of an NTHi DeltavapBC-1 strain complemented in cis with the TA module containing a mutated or wild-type toxin at an ectopic site on the chromosome. This enabled the analysis of the effect of PIN domain toxin mutants in tandem with their wild-type antitoxin under the control of the vapBC-1 native promoter and in single copy. This is the first report of a system facilitating the study of TA mutant operons in the background of NTHi during infections of primary human tissues ex vivo IMPORTANCE: Herein the crystal structure of the VapBC-1 complex from nontypeable Haemophilus influenzae (NTHi) is described. Our results show that some of the mutations in the PIN domain of the VapC-1 toxin were associated with decreased toxicity in E. coli, but the mutants retained the ability to homodimerize and to heterodimerize with the wild-type cognate antitoxin, VapB-1. A new system was designed and constructed to quantify the effects of these mutations on NTHi survival during infections of primary human tissues ex vivo Any mutation to a conserved amino acid in the PIN domain significantly decreased the number of survivors compared to the in cis wild-type toxin under the same conditions. Crystal structure of VapBC-1 from nontypeable Haemophilus influenzae and the effect of PIN domain mutations on survival during infection.,Molinaro AL, Kashipathy MM, Lovell S, Battaile KP, Coussens NP, Shen M, Daines DA J Bacteriol. 2019 Apr 1. pii: JB.00026-19. doi: 10.1128/JB.00026-19. PMID:30936373 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribonuclease 3D structures

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