5F5E

The Crystal Structure of MLL1 SET domain with N3816I/Q3867L mutation

Summary for 5F5E

• Entry DOI: 10.2210/pdb5f5e/pdb
• Related: 5F59 5F6K 5F6L
• Descriptor: Histone-lysine N-methyltransferase 2A, ZINC ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• Functional Keywords: histone methyltransferase, histone methylation, set domain, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus . MLL cleavage product N320: Nucleus. MLL cleavage product C180: Nucleus: Q03164
• Total number of polymer chains: 1
• Total formula weight: 18693.01

Authors

Li, Y.,Lei, M.,Chen, Y. (deposition date: 2015-12-04, release date: 2016-02-24, Last modification date: 2023-11-08)

Primary citation

Li, Y.,Han, J.,Zhang, Y.,Cao, F.,Liu, Z.,Li, S.,Wu, J.,Hu, C.,Wang, Y.,Shuai, J.,Chen, J.,Cao, L.,Li, D.,Shi, P.,Tian, C.,Zhang, J.,Dou, Y.,Li, G.,Chen, Y.,Lei, M.
Structural basis for activity regulation of MLL family methyltransferases.
Nature, 530:447-452, 2016

PubMed Abstract: The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A and SET1B) specifically methylate histone 3 Lys4, and have pivotal roles in the transcriptional regulation of genes involved in haematopoiesis and development. The methyltransferase activity of MLL1, by itself severely compromised, is stimulated by the three conserved factors WDR5, RBBP5 and ASH2L, which are shared by all MLL family complexes. However, the molecular mechanism of how these factors regulate the activity of MLL proteins still remains poorly understood. Here we show that a minimized human RBBP5-ASH2L heterodimer is the structural unit that interacts with and activates all MLL family histone methyltransferases. Our structural, biochemical and computational analyses reveal a two-step activation mechanism of MLL family proteins. These findings provide unprecedented insights into the common theme and functional plasticity in complex assembly and activity regulation of MLL family methyltransferases, and also suggest a universal regulation mechanism for most histone methyltransferases.

PubMed: 26886794
DOI: 10.1038/nature16952

Experimental method

X-RAY DIFFRACTION (1.802 Å)