The SMC-family Wadjet complex protects bacteria from plasmid transformation by recognition and cleavage of closed-circular DNA

Deep, Amar; Gu, Yajie; Gao, Yongqi; Ego, Kaori M.; Herzik, Mark A.; Zhou, Huilin; Corbett, K.D.

doi:10.1016/j.molcel.2022.09.008

Cited by 75 publications

(102 citation statements)

References 69 publications

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“…MksG shares the TOPRIM fold of Topo VI. These data are supported by very recent publications of Wadjet systems from Pseudomonas aeruginoasa PA14 and E. coli GF4-3 ( 63 , 76 ). In these publications the corresponding JetD (MksG) was also shown to be an endonuclease.…”

Section: Discussionsupporting

confidence: 82%

“…( D ) A model of a double-stranded DNA molecule was positioned above the two active sites of MksG to visualize a possible DNA binding mode. ( E ) Surface representation of the closed conformation of the JetD dimer ( 63 ) incompatible with DNA binding (PDB code: 7TIL).…”

Section: Resultsmentioning

confidence: 99%

“…The only tyrosine within reasonable distance for a putative catalytic role is Tyr258 (Figure 2C ), located within the TOPRIM domain. Interestingly from the DALI search on the AF2 database, several eukaryotic homologs of the Spo11 family have a conserved Tyr in the same position, and this residue seems to be conserved in other actinobacterial homologs but not in Topo VIA or JetD ( 63 ). For JetD, two conserved glutamate residues have been proposed as alternative nucleophiles which correspond to the conserved E349 and E351 in the MksG structure (Figure 2B and Supplementary Figure S4 ).…”

Section: Resultsmentioning

confidence: 99%

“…The N-terminal domain of MksG might act as a DNA clamp, helping to position or recognize the plasmid DNA. Interestingly in the recently determined structure of the Wadjet nuclease subunit JetD from Pseudomonas aeruginosa ( 63 ), the MksG homolog is found in a closed conformation (Figure 2E ) that would be incompatible with DNA binding. Further experiments will be required to understand how these open and closed conformations of MksG and JetD could be regulated.…”

Section: Discussionmentioning

confidence: 98%

See 3 more Smart Citations

The MksG nuclease is the executing part of the bacterial plasmid defense system MksBEFG

Weiss

Giacomelli

Assaya

et al. 2023

Nucleic Acids Research

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Cells are continuously facing the risk of taking up foreign DNA that can compromise genomic integrity. Therefore, bacteria are in a constant arms race with mobile genetic elements such as phages, transposons and plasmids. They have developed several active strategies against invading DNA molecules that can be seen as a bacterial ‘innate immune system’. Here, we investigated the molecular arrangement of the Corynebacterium glutamicum MksBEFG complex, which is homologous to the MukBEF condensin system. We show here that MksG is a nuclease that degrades plasmid DNA. The crystal structure of MksG revealed a dimeric assembly through its C-terminal domain that is homologous to the TOPRIM domain of the topoisomerase II family of enzymes and contains the corresponding ion binding site essential for DNA cleavage in topoisomerases. The MksBEF subunits exhibit an ATPase cycle in vitro and we reason that this reaction cycle, in combination with the nuclease activity provided by MksG, allows for processive degradation of invading plasmids. Super-resolution localization microscopy revealed that the Mks system is spatially regulated via the polar scaffold protein DivIVA. Introduction of plasmids results in an increase in DNA bound MksG, indicating an activation of the system in vivo.

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Section: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

See 2 more Smart Citations

The MksG nuclease is the executing part of the bacterial plasmid defense system MksBEFG

Weiss

Giacomelli

Assaya

et al. 2023

Nucleic Acids Research

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show abstract

“…Such a split is strongly supported by the Grishin plot (Figure 2C). Another example of such obligated splitting is target T1121, the Wadjet nuclease subunit JetD 24 . It is a homo-dimeric protein (Figure 3A) containing two domains that are flexibly linked and whose relative orientation differs in the two chains (Figure 3B).…”

Section: Multidomain-targets Requiring Splitting (20)mentioning

confidence: 99%

To split or not to split: CASP15 targets and their processing into tertiary structure evaluation units

Kryshtafovych

Rigden

2023

Preprint

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Processing of CASP15 targets into evaluation units (EUs) and assigning them to evolutionary-based prediction classes is presented in this study. The targets were first split into structural domains based on compactness and similarity to other proteins. Models were then evaluated against these domains and their combinations. The domains were joined into larger EUs if predictors’ performance on the combined units was similar to that on individual domains. Alternatively, if most predictors performed better on the individual domains, then they were retained as EUs. As a result, 112 evaluation units were created from 77 tertiary structure prediction targets. The EUs were assigned to four prediction classes roughly corresponding to target difficulty categories in previous CASPs: TBM (template-based modeling, easy or hard), FM (free modeling), and the TBM/FM overlap category. More than a third of CASP15 EUs were attributed to the historically most challenging FM class, where homology or structural analogy to proteins of known fold cannot be detected.

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The immune system of prokaryotes: potential applications and implications for gene editing

Liu,

Wang

et al. 2024

Biotechnology Journal

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Gene therapy has revolutionized the treatment of genetic diseases. Spearheading this revolution are sophisticated genome editing methods such as TALENs, ZFNs, and CRISPR‐Cas, which trace their origins back to prokaryotic immune systems. Prokaryotes have developed various antiviral defense systems to combat viral attacks and the invasion of genetic elements. The comprehension of these defense mechanisms has paved the way for the development of indispensable tools in molecular biology. Among them, restriction endonuclease originates from the innate immune system of bacteria. The CRISPR‐Cas system, a widely applied genome editing technology, is derived from the prokaryotic adaptive immune system. Single‐base editing is a precise editing tool based on CRISPR‐Cas system that involves deamination of target base. It is worth noting that prokaryotes possess deamination enzymes as part of their defense arsenal over foreign genetic material. Furthermore, prokaryotic Argonauts (pAgo) proteins, also function in anti‐phage defense, play an important role in complementing the CRISPR‐Cas system by addressing certain limitations it may have. Recent studies have also shed light on the significance of Retron, a reverse transcription transposon previously showed potential in genome editing, has also come to light in the realm of prokaryotic immunity. These noteworthy findings highlight the importance of studying prokaryotic immune system for advancing genome editing techniques. Here, both the origin of prokaryotic immunity underlying aforementioned genome editing tools, and potential applications of deaminase, pAgo protein and reverse transcriptase in genome editing among prokaryotes were introduced, thus emphasizing the fundamental mechanism and significance of prokaryotic immunity.

show abstract

The SMC-family Wadjet complex protects bacteria from plasmid transformation by recognition and cleavage of closed-circular DNA

Cited by 75 publications

References 69 publications

The MksG nuclease is the executing part of the bacterial plasmid defense system MksBEFG

The MksG nuclease is the executing part of the bacterial plasmid defense system MksBEFG

To split or not to split: CASP15 targets and their processing into tertiary structure evaluation units

The immune system of prokaryotes: potential applications and implications for gene editing

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