Structural highlights
Function
[MCRB_ECOLI] Recognizes N4- and C5-methylcytosine (and 5-hydroxy-methylcytosines) produced by a broad range of DNA methylases and appears to act against 5-methylcytosine preceded by a purine residue. Binds to DNA containing methylated cytosines; also binds to GTP. Isoform 33 kDa is less active than isoform 51 kDa and may play a role in regulating the activity of isoform 51 kDa by competing with it in DNA and protein binding abilities.
Publication Abstract from PubMed
Cytosine modifications expand the information content of genomic DNA in both eukaryotes and prokaryotes, providing means for epigenetic regulation and self versus non-self discrimination. For example, the methyl-directed restriction endonuclease McrBC recognizes and cuts invading bacteriophage DNA containing 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and N4-methylcytosine (4mC), leaving unmodified host DNA intact. Here, we present co-crystal structures of McrB-N bound to DNA oligoduplexes containing 5hmC, 5-formylcytosine (5fC) and 4mC, and characterise the relative affinity of McrB-N to various cytosine variants. We find that McrB-N flips out modified bases into a protein pocket and binds cytosine derivatives in the order of descending affinity: 4mC>5mC>5hmC>>5fC. We also show that pocket mutations alter the relative preference of McrB-N to 5mC, 5hmC and 4mC. This article is protected by copyright. All rights reserved.
Recognition of modified cytosine variants by the DNA binding domain of methyl-directed endonuclease McrBC.,Zagorskaite E, Manakova E, Sasnauskas G FEBS Lett. 2018 Sep 8. doi: 10.1002/1873-3468.13244. PMID:30194838[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zagorskaite E, Manakova E, Sasnauskas G. Recognition of modified cytosine variants by the DNA binding domain of methyl-directed endonuclease McrBC. FEBS Lett. 2018 Sep 8. doi: 10.1002/1873-3468.13244. PMID:30194838 doi:http://dx.doi.org/10.1002/1873-3468.13244
