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PDBsum entry 3lpy

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Isomerase PDB id
3lpy
Jmol
Contents
Protein chains
79 a.a.
Ligands
SO4 ×4
EPE ×2
Waters ×100

References listed in PDB file
Key reference
Title Pro isomerization in mll1 phd3-Bromo cassette connects h3k4me readout to cyp33 and hdac-Mediated repression.
Authors Z.Wang, J.Song, T.A.Milne, G.G.Wang, H.Li, C.D.Allis, D.J.Patel.
Ref. Cell, 2010, 141, 1183-1194. [DOI no: 10.1016/j.cell.2010.05.016]
PubMed id 20541251
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.
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