7ZEZ

Trimolecular complex Cyp33-RRMdelta alpha : MLL1-PHD3 : H3K4me3

Summary for 7ZEZ

• Entry DOI: 10.2210/pdb7zez/pdb
• Related: 7ZEV 7ZEW 7ZEX 7ZEY
• NMR Information: BMRB: 34728
• Descriptor: Isoform 3 of Peptidyl-prolyl cis-trans isomerase E, MLL cleavage product N320, Histone H3, ... (4 entities in total)
• Functional Keywords: rrm, rna binding protein-structural protein complex, histone 3, h3k4me3, epigenetic, mll1 transcription regulation, infant leukemia, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 19325.52

Authors

Blatter, M.,Allain, F.,Meylan, C. (deposition date: 2022-03-31, release date: 2022-04-13, Last modification date: 2023-05-03)

Primary citation

Blatter, M.,Meylan, C.,Clery, A.,Giambruno, R.,Nikolaev, Y.,Heidecker, M.,Solanki, J.A.,Diaz, M.O.,Gabellini, D.,Allain, F.H.
RNA binding induces an allosteric switch in Cyp33 to repress MLL1-mediated transcription.
Sci Adv, 9:eadf5330-eadf5330, 2023

PubMed Abstract: Mixed-lineage leukemia 1 (MLL1) is a transcription activator of the HOX family, which binds to specific epigenetic marks on histone H3 through its third plant homeodomain (PHD3) domain. Through an unknown mechanism, MLL1 activity is repressed by cyclophilin 33 (Cyp33), which binds to MLL1 PHD3. We determined solution structures of Cyp33 RNA recognition motif (RRM) free, bound to RNA, to MLL1 PHD3, and to both MLL1 and the histone H3 lysine N6-trimethylated. We found that a conserved α helix, amino-terminal to the RRM domain, adopts three different positions facilitating a cascade of binding events. These conformational changes are triggered by Cyp33 RNA binding and ultimately lead to MLL1 release from the histone mark. Together, our mechanistic findings rationalize how Cyp33 binding to MLL1 can switch chromatin to a transcriptional repressive state triggered by RNA binding as a negative feedback loop.

PubMed: 37075125
DOI: 10.1126/sciadv.adf5330

Experimental method

SOLUTION NMR