7zey | pdb_00007zey
Complex Cyp33-RRM : MLL1-PHD3
Structural highlights
FunctionPPIE_HUMAN PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Combines RNA-binding and PPIase activities. May be involved in muscle- and brain-specific processes. May be involved in pre-mRNA splicing. Publication Abstract from PubMedMixed-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 alpha 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. RNA binding induces an allosteric switch in Cyp33 to repress MLL1-mediated transcription.,Blatter M, Meylan C, Clery A, Giambruno R, Nikolaev Y, Heidecker M, Solanki JA, Diaz MO, Gabellini D, Allain FH Sci Adv. 2023 Apr 21;9(16):eadf5330. doi: 10.1126/sciadv.adf5330. Epub 2023 Apr , 19. PMID:37075125[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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