Summary information and primary citation
- 3q0c; SNAP-derived features in text and JSON formats;
- X-ray (2.66 Å)
- Crystal structure of suvh5 sra-fully methylated cg DNA complex in space group p6122
- Rajakumara E, Law JA, Simanshu DK, Voigt P, Johnson LM, Reinberg D, Patel DJ, Jacobsen SE (2011): "A dual flip-out mechanism for 5mC recognition by the Arabidopsis SUVH5 SRA domain and its impact on DNA methylation and H3K9 dimethylation in vivo." Genes Dev., 25, 137-152. doi: 10.1101/gad.1980311.
- Cytosine DNA methylation is evolutionarily ancient, and in eukaryotes this epigenetic modification is associated with gene silencing. Proteins with SRA (SET- or RING-associated) methyl-binding domains are required for the establishment and/or maintenance of DNA methylation in both plants and mammals. The 5-methyl-cytosine (5mC)-binding specificity of several SRA domains have been characterized, and each one has a preference for DNA methylation in different sequence contexts. Here we demonstrate through mobility shift assays and calorimetric measurements that the SU(VAR)3-9 HOMOLOG 5 (SUVH5) SRA domain differs from other SRA domains in that it can bind methylated DNA in all contexts to similar extents. Crystal structures of the SUVH5 SRA domain bound to 5mC-containing DNA in either the fully or hemimethylated CG context or the methylated CHH context revealed a dual flip-out mechanism where both the 5mC and a base (5mC, C, or G, respectively) from the partner strand are simultaneously extruded from the DNA duplex and positioned within binding pockets of individual SRA domains. Our structure-based in vivo studies suggest that a functional SUVH5 SRA domain is required for both DNA methylation and accumulation of the H3K9 dimethyl modification in vivo, suggesting a role for the SRA domain in recruitment of SUVH5 to genomic loci.
- The contacts include paired nucleotides (mostly a G in Watson-Crick G-C pairing), and
amino-acids within a 4.5-A distance cutoff to base atoms of 5mC.
- The structure is oriented in the base reference frame of 5mC, allowing for easy comparison
and direct superimposition between entries.
- The black sphere (•) denotes the 5-methyl carbon atom in 5mC.
|No. 1 C.5CM5:
stacking-with-X.TYR416 stacking-with-X.TYR428 not-WC-paired not-in-duplex
|No. 2 B.5CM5:
stacking-with-A.TYR416 stacking-with-A.TYR428 not-WC-paired not-in-duplex