5mC interactions in PDB entry 3SSC auto-curated with SNAP

Last updated on 2019-09-30 by Xiang-Jun Lu <xiangjun@x3dna.org>. The block schematics were created with DSSR and rendered using PyMOL.

Summary information and primary citation [schematics · contacts · top · homepage · tutorial]

DNA binding protein-DNA
X-ray (2.1 Å)
DNA binding domain of restriction endonuclease bound to DNA
List of 2 5mC-amino acid contacts:
  1. C.5CM6: stacking-with-B.TYR117 not-WC-paired not-in-duplex
  2. D.5CM6: stacking-with-A.TYR117 not-WC-paired not-in-duplex
direct SNAP output · DNAproDB 2.0
Sukackaite, R., Grazulis, S., Tamulaitis, G., Siksnys, V.: (2012) "The recognition domain of the methyl-specific endonuclease McrBC flips out 5-methylcytosine." Nucleic Acids Res., 40, 7552-7562.
DNA cytosine methylation is a widespread epigenetic mark. Biological effects of DNA methylation are mediated by the proteins that preferentially bind to 5-methylcytosine (5mC) in different sequence contexts. Until now two different structural mechanisms have been established for 5mC recognition in eukaryotes; however, it is still unknown how discrimination of the 5mC modification is achieved in prokaryotes. Here we report the crystal structure of the N-terminal DNA-binding domain (McrB-N) of the methyl-specific endonuclease McrBC from Escherichia coli. The McrB-N protein shows a novel DNA-binding fold adapted for 5mC-recognition. In the McrB-N structure in complex with methylated DNA, the 5mC base is flipped out from the DNA duplex and positioned within a binding pocket. Base flipping elegantly explains why McrBC system restricts only T4-even phages impaired in glycosylation [Luria, S.E. and Human, M.L. (1952) A nonhereditary, host-induced variation of bacterial viruses. J. Bacteriol., 64, 557-569]: flipped out 5-hydroxymethylcytosine is accommodated in the binding pocket but there is no room for the glycosylated base. The mechanism for 5mC recognition employed by McrB-N is highly reminiscent of that for eukaryotic SRA domains, despite the differences in their protein folds.

Base-block schematics in six views [summary · contacts · top · homepage · tutorial]

List of 2 5mC-amino acid contacts [summary · schematics · top · homepage · tutorial]

No. 1 C.5CM6: download PDB file for the 5mC entry
stacking-with-B.TYR117 not-WC-paired not-in-duplex
No. 2 D.5CM6: download PDB file for the 5mC entry
stacking-with-A.TYR117 not-WC-paired not-in-duplex