3kh2
From Proteopedia
Crystal structure of the P1 bacteriophage Doc toxin (F68S) in complex with the Phd antitoxin (L17M/V39A). Northeast Structural Genomics targets ER385-ER386
Structural highlights
Function[DOC_BPP1] Toxic component of a toxin-antitoxin (TA) module. Overexpression results in inhibition of growth in liquid cultures and a decrease in colony formation by inhibiting translation, stabilizing mRNA and polysomes; these effects are overcome by concomitant expression of antitoxin phd. Binds 70S ribosomes and the 30S ribosomal subunits, the binding site is the same as for the antibiotic hygromycin B. Bacteriophage P1 lysogenizes bacteria as a low-copy number plasmid. Doc and phd proteins function in unison to stabilize plasmid number by inducing a lethal response to P1 plasmid prophage loss. Overexpression of doc can induce the mRNA interferase activity of RelE in vivo.[1] [2] Antitoxin phd binds to its own promoter repressing its expression; toxin doc acts as a corepressor or derepressor depending on the ratio, repressing or inducing expression.[3] [4] [PHD_BPP1] Antitoxin component of a toxin-antitoxin (TA) module. A labile antitoxin that binds to the doc toxin and neutralizes its toxic effect. Bacteriophage P1 lysogenizes bacteria as a low-copy number plasmid. Phd and doc proteins function in unison to stabilize plasmid number by inducing a lethal response to P1 plasmid prophage loss.[5] [6] Binds to its own promoter repressing its expression; toxin doc acts as a corepressor or derepressor depending on the ratio, repressing or inducing expression.[7] [8] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBacterial toxin-antitoxin (TA) systems serve a variety of physiological functions including regulation of cell growth and maintenance of foreign genetic elements. Sequence analyses suggest that TA families are linked by complex evolutionary relationships reflecting likely swapping of functional domains between different TA families. Our crystal structures of Phd-Doc from bacteriophage P1, the HigA antitoxin from Escherichia coli CFT073, and YeeU of the YeeUWV systems from E. coli K12 and Shigella flexneri confirm this inference and reveal additional, unanticipated structural relationships. The growth-regulating Doc toxin exhibits structural similarity to secreted virulence factors that are toxic for eukaryotic target cells. The Phd antitoxin possesses the same fold as both the YefM and NE2111 antitoxins that inhibit structurally unrelated toxins. YeeU, which has an antitoxin-like activity that represses toxin expression, is structurally similar to the ribosome-interacting toxins YoeB and RelE. These observations suggest extensive functional exchanges have occurred between TA systems during bacterial evolution. Crystal structures of Phd-Doc, HigA, and YeeU establish multiple evolutionary links between microbial growth-regulating toxin-antitoxin systems.,Arbing MA, Handelman SK, Kuzin AP, Verdon G, Wang C, Su M, Rothenbacher FP, Abashidze M, Liu M, Hurley JM, Xiao R, Acton T, Inouye M, Montelione GT, Woychik NA, Hunt JF Structure. 2010 Aug 11;18(8):996-1010. PMID:20696400[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||||
