4Z4P

Structure of the MLL4 SET Domain

Summary for 4Z4P

• Entry DOI: 10.2210/pdb4z4p/pdb
• Descriptor: Histone-lysine N-methyltransferase 2D, ZINC ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• Functional Keywords: transferase, set domain methyltransferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : O14686
• Total number of polymer chains: 1
• Total formula weight: 20154.17

Authors

Zhang, Z.,Mittal, A.,Reid, J.,Reich, S.,Gamblin, S.J.,Wilson, J.R. (deposition date: 2015-04-02, release date: 2015-09-09, Last modification date: 2024-01-10)

Primary citation

Zhang, Y.,Mittal, A.,Reid, J.,Reich, S.,Gamblin, S.J.,Wilson, J.R.
Evolving Catalytic Properties of the MLL Family SET Domain.
Structure, 23:1921-1933, 2015

PubMed Abstract: Methylation of histone H3 lysine-4 is a hallmark of chromatin associated with active gene expression. The activity of H3K4-specific modification enzymes, in higher eukaryotes the MLL (or KMT2) family, is tightly regulated. The MLL family has six members, each with a specialized function. All contain a catalytic SET domain that associates with a core multiprotein complex for activation. These SET domains segregate into three classes that correlate with the arrangement of targeting domains that populate the rest of the protein. Here we show that, unlike MLL1, the MLL4 SET domain retains significant activity without the core complex. We also present the crystal structure of an inactive MLL4-tagged SET domain construct and describe conformational changes that account for MLL4 intrinsic activity. Finally, our structure explains how the MLL SET domains are able to add multiple methyl groups to the target lysine, despite having the sequence characteristics of a classical monomethylase.

PubMed: 26320581
DOI: 10.1016/j.str.2015.07.018

Experimental method

X-RAY DIFFRACTION (2.2 Å)