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3lpy

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3lpy, resolution 2.00Å ()
Ligands: ,
Gene: PPIE, CYP33 (Homo sapiens)
Activity: Peptidylprolyl isomerase, with EC number 5.2.1.8


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Crystal structure of the RRM domain of CyP33

Publication Abstract from PubMed

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.

Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression., Wang Z, Song J, Milne TA, Wang GG, Li H, Allis CD, Patel DJ, Cell. 2010 Jun 25;141(7):1183-94. Epub 2010 Jun 10. PMID:20541251

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3lpy is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Wang Z, Song J, Milne TA, Wang GG, Li H, Allis CD, Patel DJ. Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression. Cell. 2010 Jun 25;141(7):1183-94. Epub 2010 Jun 10. PMID:20541251 doi:10.1016/j.cell.2010.05.016

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