2W5Z

Ternary Complex of the Mixed Lineage Leukaemia (MLL1) SET Domain with the cofactor product S-Adenosylhomocysteine and histone peptide.

Summary for 2W5Z

• Entry DOI: 10.2210/pdb2w5z/pdb
• Related: 2AGH 2J2S 2W5Y
• Descriptor: HISTONE-LYSINE N-METHYLTRANSFERASE HRX, HISTONE PEPTIDE, ZINC ION, ... (6 entities in total)
• Functional Keywords: transcription regulation, chromosomal rearrangement, protein lysine methyltransferase, proto-oncogene, phosphoprotein, ubl conjugation, s-adenosyl-l-methionine, mixed lineage leukaemia, polymorphism, transcription, metal-binding, zinc-finger, dna-binding, bromodomain, transferase, methyltransferase, chromatin regulator, alternative splicing, histone modification, mll1, zinc, kmt2a, nucleus, apoptosis, set domain
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus. MLL cleavage product N320: Nucleus. MLL cleavage product C180: Nucleus: Q03164
• Total number of polymer chains: 2
• Total formula weight: 23939.70

Authors

Southall, S.M.,Wong, P.S.,Odho, Z.,Roe, S.M.,Wilson, J.R. (deposition date: 2008-12-15, release date: 2009-02-10, Last modification date: 2011-07-13)

Primary citation

Southall, S.M.,Wong, P.S.,Odho, Z.,Roe, S.M.,Wilson, J.R.
Structural Basis for the Requirement of Additional Factors for Mll1 Set Domain Activity and Recognition of Epigenetic Marks.
Mol.Cell, 33:181-, 2009

PubMed Abstract: The mixed-lineage leukemia protein MLL1 is a transcriptional regulator with an essential role in early development and hematopoiesis. The biological function of MLL1 is mediated by the histone H3K4 methyltransferase activity of the carboxyl-terminal SET domain. We have determined the crystal structure of the MLL1 SET domain in complex with cofactor product AdoHcy and a histone H3 peptide. This structure indicates that, in order to form a well-ordered active site, a highly variable but essential component of the SET domain must be repositioned. To test this idea, we compared the effect of the addition of MLL complex members on methyltransferase activity and show that both RbBP5 and Ash2L but not Wdr5 stimulate activity. Additionally, we have determined the effect of posttranslational modifications on histone H3 residues downstream and upstream from the target lysine and provide a structural explanation for why H3T3 phosphorylation and H3K9 acetylation regulate activity.

PubMed: 19187761
DOI: 10.1016/J.MOLCEL.2008.12.029

Experimental method

X-RAY DIFFRACTION (2.2 Å)