4L58

Crystal structure of the MLL5 PHD finger in complex with H3K4me3

Summary for 4L58

• Entry DOI: 10.2210/pdb4l58/pdb
• Descriptor: Histone-lysine N-methyltransferase MLL5, Histone H3 peptide, ZINC ION, ... (4 entities in total)
• Functional Keywords: transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus speckle: Q8IZD2
• Total number of polymer chains: 2
• Total formula weight: 9667.88

Authors

Tong, Q.,Ali, M.,Kutateladze, T.G. (deposition date: 2013-06-10, release date: 2013-06-26, Last modification date: 2013-07-24)

Primary citation

Ali, M.,Rincon-Arano, H.,Zhao, W.,Rothbart, S.B.,Tong, Q.,Parkhurst, S.M.,Strahl, B.D.,Deng, L.W.,Groudine, M.,Kutateladze, T.G.
Molecular basis for chromatin binding and regulation of MLL5.
Proc.Natl.Acad.Sci.USA, 110:11296-11301, 2013

PubMed Abstract: The human mixed-lineage leukemia 5 (MLL5) protein mediates hematopoietic cell homeostasis, cell cycle, and survival; however, the molecular basis underlying MLL5 activities remains unknown. Here, we show that MLL5 is recruited to gene-rich euchromatic regions via the interaction of its plant homeodomain finger with the histone mark H3K4me3. The 1.48-Å resolution crystal structure of MLL5 plant homeodomain in complex with the H3K4me3 peptide reveals a noncanonical binding mechanism, whereby K4me3 is recognized through a single aromatic residue and an aspartate. The binding induces a unique His-Asp swapping rearrangement mediated by a C-terminal α-helix. Phosphorylation of H3T3 and H3T6 abrogates the association with H3K4me3 in vitro and in vivo, releasing MLL5 from chromatin in mitosis. This regulatory switch is conserved in the Drosophila ortholog of MLL5, UpSET, and suggests the developmental control for targeting of H3K4me3. Together, our findings provide first insights into the molecular basis for the recruitment, exclusion, and regulation of MLL5 at chromatin.

PubMed: 23798402
DOI: 10.1073/pnas.1310156110

Experimental method

X-RAY DIFFRACTION (1.48 Å)