3LQH

Crystal structure of MLL1 PHD3-Bromo in the free form

Summary for 3LQH

• Entry DOI: 10.2210/pdb3lqh/pdb
• Related: 3LQI 3LQJ
• Descriptor: Histone-lysine N-methyltransferase MLL, ZINC ION (3 entities in total)
• Functional Keywords: phd finger, bromodomain, mll1, leukemia, apoptosis, chromatin regulator, dna-binding, isopeptide bond, metal-binding, methyltransferase, nucleus, phosphoprotein, proto-oncogene, s-adenosyl-l-methionine, transcription, transcription regulation, transferase, zinc-finger
• 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: 1
• Total formula weight: 21436.11

Authors

Wang, Z.,Patel, D.J. (deposition date: 2010-02-09, release date: 2010-07-07, Last modification date: 2024-02-21)

Primary citation

Wang, Z.,Song, J.,Milne, T.A.,Wang, G.G.,Li, H.,Allis, C.D.,Patel, D.J.
Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression.
Cell(Cambridge,Mass.), 141:1183-1194, 2010

PubMed Abstract: The MLL1 gene is a frequent target for recurrent chromosomal translocations, resulting in transformation of hematopoietic precursors into leukemia stem cells. Here, we report on structure-function studies that elucidate molecular events in MLL1 binding of histone H3K4me3/2 marks and recruitment of the cyclophilin CyP33. CyP33 contains a PPIase and a RRM domain and regulates MLL1 function through HDAC recruitment. We find that the PPIase domain of CyP33 regulates the conformation of MLL1 through proline isomerization within the PHD3-Bromo linker, thereby disrupting the PHD3-Bromo interface and facilitating binding of the MLL1-PHD3 domain to the CyP33-RRM domain. H3K4me3/2 and CyP33-RRM target different surfaces of MLL1-PHD3 and can bind simultaneously to form a ternary complex. Furthermore, the MLL1-CyP33 interaction is required for repression of HOXA9 and HOXC8 genes in vivo. Our results highlight the role of PHD3-Bromo cassette as a regulatory platform, orchestrating MLL1 binding of H3K4me3/2 marks and cyclophilin-mediated repression through HDAC recruitment.

PubMed: 20541251
DOI: 10.1016/j.cell.2010.05.016

Experimental method

X-RAY DIFFRACTION (1.72 Å)