IPR025789
Histone-lysine N-methyltransferase DOT1 domain
InterPro entry
Short name | DOT1_dom |
Overlapping homologous superfamilies |
Description
This entry represents the DOT1 domain.
The Dot1 protein (Dot1p) is an histone-lysine N-methyltransferase (
2.1.1.360) that methylates lysine 79 (Lys-79) of histone H3. It was first
identified as a Disruptor Of Telomeric silencing in yeast where Dot1p is implicated in gene silencing and localization of the Silent Information Regulator (SIR) complex; in higher eukaryotes the methylation carried out by this enzyme may be used for differentiating chromatin domains. Unlike other histone-lysine methyltransferases (HKMTs), Dot1p displays a Rossmann-like (Class I) S-adenosyl-L-methyionine (SAM)-dependent MT fold while other HKMTs contain the SET domain and hence belong to a whole different structural class
[1, 2, 3].
Whereas most HKMTs, such as Suvar3-9 methylate Lys on the N-terminal tails of histones that stick out from the nucleosome, Dot1p substrate (Lys-79 of histone H3) is located in the conserved histone core, in a short turn connecting the first and second helices, exposed on the nucleosome disk
surface
[1, 2]. In order for Lys-79 of H3 to be methylated by Dot1p, another lysine, Lys-123 of histone H2B, needs to be ubiquitinated. A possible reason put forward for this requirement is that the ubiquitination may create a space between adjacent nucleosomes, permitting access of Dot1p to its substrate
[1, 2]. In yeast, different states of methylation on Lys-79 of histone H3 (unmodified, mono-, di- and trimethylated) co-exist at the same time, but no clear function is associated with these different methylation states
[1].
The structure of the evolutionary conserved core of Dot1p, the DOT1 domain, has first been described for the yeast Dot1p in complex with
S-adenosyl-L-homocysteine (AdoHcy) and then for the human Dot1-like protein (Dot1Lp) in complex with SAM. The DOT1 domain is about 300-350 amino acids long and is usually located at either of the extremities of the protein sequence: it stands at the C terminus of the yeast Dot1p and at the N terminus of the human Dot1Lp
[1, 2]. DOT1 displays a rather elongated structure and can be subdivided into two parts: the N- and the C-terminal subdomains
[2]. The N-terminal part is made up of five α-helices and two pairs of short β-strand hairpins. The C-terminal part displays a Rossmann-like fold: it consists in a seven-stranded β-sheet tucked by five α-helices (three helices on one
side of the sheet and two on the other), the sheet contains a central topological switchpoint resulting in a deep pocket where SAM is bound. The two
subdomains are linked covalently by a loop. Altogether the SAM binding pocket is formed by five segments of the DOT1 domain of which four are located in the C-terminal substructure of the DOT1 domain and one in the loop connecting both parts; two of these segments are conserved across different Class I SAM-dependent MTs
[2].
References
1.Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase. Sawada K, Yang Z, Horton JR, Collins RE, Zhang X, Cheng X. J. Biol. Chem. 279, 43296-306, (2004). View articlePMID: 15292170
2.Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. Min J, Feng Q, Li Z, Zhang Y, Xu RM. Cell 112, 711-23, (2003). View articlePMID: 12628190
3.Characterization of the grappa gene, the Drosophila histone H3 lysine 79 methyltransferase. Shanower GA, Muller M, Blanton JL, Honti V, Gyurkovics H, Schedl P. Genetics 169, 173-84, (2005). View articlePMID: 15371351
GO terms
biological process
- None
molecular function
cellular component
- None
Cross References
ENZYME