PMID- 21306995
OWN - NLM
STAT- MEDLINE
DCOM- 20110823
LR  - 20211020
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 39
IP  - 11
DP  - 2011 Jun
TI  - A novel immunity system for bacterial nucleic acid degrading toxins and its 
      recruitment in various eukaryotic and DNA viral systems.
PG  - 4532-52
LID - 10.1093/nar/gkr036 [doi]
AB  - The use of nucleases as toxins for defense, offense or addiction of selfish 
      elements is widely encountered across all life forms. Using sensitive sequence 
      profile analysis methods, we characterize a novel superfamily (the SUKH 
      superfamily) that unites a diverse group of proteins including Smi1/Knr4, PGs2, 
      FBXO3, SKIP16, Syd, herpesviral US22, IRS1 and TRS1, and their bacterial 
      homologs. Using contextual analysis we present evidence that the bacterial 
      members of this superfamily are potential immunity proteins for a variety of 
      toxin systems that also include the recently characterized contact-dependent 
      inhibition (CDI) systems of proteobacteria. By analyzing the toxin proteins 
      encoded in the neighborhood of the SUKH superfamily we predict that they possess 
      domains belonging to diverse nuclease and nucleic acid deaminase families. These 
      include at least eight distinct types of DNases belonging to HNH/EndoVII- and 
      restriction endonuclease-fold, and RNases of the EndoU-like and colicin E3-like 
      cytotoxic RNases-folds. The N-terminal domains of these toxins indicate that they 
      are extruded by several distinct secretory mechanisms such as the two-partner 
      system (shared with the CDI systems) in proteobacteria, ESAT-6/WXG-like 
      ATP-dependent secretory systems in Gram-positive bacteria and the conventional 
      Sec-dependent system in several bacterial lineages. The hedgehog-intein domain 
      might also release a subset of toxic nuclease domains through auto-proteolytic 
      action. Unlike classical colicin-like nuclease toxins, the overwhelming majority 
      of toxin systems with the SUKH superfamily is chromosomally encoded and appears 
      to have diversified through a recombination process combining different 
      C-terminal nuclease domains to N-terminal secretion-related domains. Across the 
      bacterial superkingdom these systems might participate in discriminating ;self' 
      or kin from ;non-self' or non-kin strains. Using structural analysis we 
      demonstrate that the SUKH domain possesses a versatile scaffold that can be used 
      to bind a wide range of protein partners. In eukaryotes it appears to have been 
      recruited as an adaptor to regulate modification of proteins by ubiquitination or 
      polyglutamylation. Similarly, another widespread immunity protein from these 
      toxin systems, namely the suppressor of fused (SuFu) superfamily has been 
      recruited for comparable roles in eukaryotes. In animal DNA viruses, such as 
      herpesviruses, poxviruses, iridoviruses and adenoviruses, the ability of the SUKH 
      domain to bind diverse targets has been deployed to counter diverse anti-viral 
      responses by interacting with specific host proteins.
FAU - Zhang, Dapeng
AU  - Zhang D
AD  - National Center for Biotechnology Information, National Library of Medicine, 
      National Institutes of Health, Bethesda, MD 20894, USA.
FAU - Iyer, Lakshminarayan M
AU  - Iyer LM
FAU - Aravind, L
AU  - Aravind L
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20110208
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Bacterial Proteins)
RN  - 0 (Bacterial Toxins)
RN  - 0 (SMI1 protein, S cerevisiae)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 3.1.- (Deoxyribonucleases)
RN  - EC 3.1.- (Ribonucleases)
RN  - EC 3.1.21.- (DNA Restriction Enzymes)
SB  - IM
MH  - Amino Acid Sequence
MH  - Bacteria/enzymology
MH  - Bacterial Proteins/*chemistry/genetics/metabolism
MH  - Bacterial Toxins/*chemistry/genetics/metabolism
MH  - Conserved Sequence
MH  - DNA Restriction Enzymes/chemistry
MH  - DNA Viruses/genetics
MH  - Deoxyribonucleases/*chemistry
MH  - Microbial Interactions
MH  - Molecular Sequence Data
MH  - Protein Structure, Tertiary
MH  - Protein Transport
MH  - Ribonucleases/*chemistry
MH  - Saccharomyces cerevisiae Proteins/chemistry
MH  - Sequence Alignment
MH  - Sequence Analysis, Protein
MH  - Structure-Activity Relationship
MH  - Transcription Factors/chemistry
PMC - PMC3113570
EDAT- 2011/02/11 06:00
MHDA- 2011/08/24 06:00
PMCR- 2011/02/08
CRDT- 2011/02/11 06:00
PHST- 2011/02/11 06:00 [entrez]
PHST- 2011/02/11 06:00 [pubmed]
PHST- 2011/08/24 06:00 [medline]
PHST- 2011/02/08 00:00 [pmc-release]
AID - gkr036 [pii]
AID - 10.1093/nar/gkr036 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2011 Jun;39(11):4532-52. doi: 10.1093/nar/gkr036. Epub 2011 
      Feb 8.