PDBsum entry 3lqi

Transferase

PDB id: 3lqi

Contents

Protein chain

176 a.a.

Ligands

ALA-ARG-THR-MLY-GLN-THR

ALA-ARG-THR-MLY-GLN-THR-ALA

ALA-ARG-THR-MLY-GLN-THR-ALA-ARG-LYS

Metals

_ZN ×6

Waters ×369

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.
• 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.