The SET and MYND Domain (SMYD) proteins comprise a unique family of multi-domain SET histone methyltransferases that are implicated in human cancer progression. Here we report an analysis of the crystal structure of the full length human SMYD3 in a complex with an analog of the S-adenosyl methionine (SAM) methyl donor cofactor. The structure revealed an overall compact architecture in which the "split-SET" domain adopts a canonical SET domain fold and closely assembles with a Zn-binding MYND domain and a C-terminal superhelical 9 α-helical bundle similar to that observed for the mouse SMYD1 structure. Together, these structurally interlocked domains impose a highly confined binding pocket for histone substrates, suggesting a regulated mechanism for its enzymatic activity. Our mutational and biochemical analyses confirm regulatory roles of the unique structural elements both inside and outside the core SET domain and establish a previously undetected preference for trimethylation of H4K20. © 2011 Foreman et al.
CITATION STYLE
Foreman, K. W., Brown, M., Park, F., Emtage, S., Harriss, J., Das, C., … Tucker, P. (2011). Structural and functional profiling of the human histone methyltransferase SMYD3. PLoS ONE, 6(7). https://doi.org/10.1371/journal.pone.0022290
Mendeley helps you to discover research relevant for your work.