DISARM
Description
DISARM (Defense Island System Associated with Restriction-Modification) is a defense system widespread in prokaryotes, encoded by a 5-gene cassette. DISARM provides broad protection against double-stranded DNA phages, including siphophages, myophages, and podophages (N/A, N/A) .
It was reported to restrict incoming phage DNA and methylate the bacterial host DNA, which could be responsible for self from non-self discrimination (N/A) . This suggests a Restriction-Modification-like (RM-like) mechanism, yet some pieces of experimental evidence hint that DISARM acts through a novel and uncharacterized molecular mechanism (N/A, N/A) .
Molecular mechanism
DISARM allows phage adsorption but prevents phage replication. DISARM is thought to cause intracellular phage DNA decay (N/A) , but the molecular of this potential DNA degradation remains unknown.
The drmMII gene of the DISARM system from Bacillus paralicheniformis was shown to methylate bacterial DNA at CCWGG motifs when expressed in Bacillus subtilis, and in the absence of drmMII, this DISARM system appears toxic to the cells (N/A) . These observations are consistent with an RM-like mechanism, where nucleic acid degradation targets specific DNA motifs, that are methylated in the bacterial chromosome to prevent auto-immunity.
Yet this system was also shown to protect against phages whose genomes are exempt from CCWGG motifs (N/A) . Moreover, a recent study reports that the absence of methylases (DrmMI or DrmMII) of the DISARM system from a Serratia sp. does not result in autoimmunity (N/A) . Both these results suggest additional phage DNA recognition mechanisms.
Hints of these additional mechanisms can be found in recent structural studies, which show that DrmA and DrmB form a complex that can bind single-stranded DNA (N/A) . Moreover, the DrmAB complex seems to exhibit strong ATPase activity in the presence of unmethylated DNA, and reduced ATPase activity in the presence of a methylated DNA substrate (N/A) . Finally, binding of unmethylated single-stranded DNA appears to mediate major conformational change of the complex, which was hypothesized to be responsible for downstream DISARM activation (N/A) .
Example of genomic structure
DISARM is encoded by three core genes: drmA (encoding for a protein containing a putative helicase domain), drmB (encoding for a protein containing a putative helicase-associated domain), and drmC (encoding for a protein containing a phospholipase D/nuclease domain) (N/A)
These three core genes are accompanied by a methyltransferase, which can be either an adenine methylase (drmMI) for class 1 DISARM systems or a cytosine methylase (drmMII) for DISARM class 2. Both classes also encode an additional gene (drmD for class 1, and drmE for class 2).
A total of 2 subsystems have been described for the DISARM system.
Here are some examples found in the RefSeq database:
The DISARM_1 system in Burkholderia pseudomallei (GCF_001887555.1, NZ_CP016910) is composed of 5 proteins drmD (WP_043276582.1) drmMI (WP_071897987.1) drmA (WP_024430133.1) drmB (WP_043276578.1) drmC (WP_229202442.1)
The DISARM_2 system in Bacillus halotolerans (GCF_018417515.1, NZ_CP070976) is composed of 5 proteins drmMII (WP_213418185.1) drmC (WP_213418186.1) drmB (WP_213418187.1) drmA (WP_213418188.1) drmE (WP_213418189.1)
Distribution of the system among prokaryotes
Structure
Group | Structure | Foldseek | System | Gene name | Subtype | Proteins in structure | System genes | Prediction type | N genes in sys | pLDDT | iptm+ptm | pDockQ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No data available | ||||||||||||