3MDF

Crystal structure of the RRM domain of Cyclophilin 33

3MDF の概要

• エントリーDOI: 10.2210/pdb3mdf/pdb
• 分子名称: Peptidyl-prolyl cis-trans isomerase E (2 entities in total)
• 機能のキーワード: rrm domain, phd finger, cyp33, mll, rna binding protein, isomerase, mrna processing, mrna splicing, nucleus, rna-binding, rotamase, spliceosome
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9UNP9
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18827.13

構造登録者

Hom, R.A.,Chang, P.Y.,Roy, S.,Mussleman, C.A.,Glass, K.C.,Seleznevia, A.I.,Gozani, O.,Ismagilov, R.F.,Cleary, M.L.,Kutateladze, T.G. (登録日: 2010-03-30, 公開日: 2010-05-12, 最終更新日: 2023-09-06)

主引用文献

Hom, R.A.,Chang, P.Y.,Roy, S.,Musselman, C.A.,Glass, K.C.,Selezneva, A.I.,Gozani, O.,Ismagilov, R.F.,Cleary, M.L.,Kutateladze, T.G.
Molecular mechanism of MLL PHD3 and RNA recognition by the Cyp33 RRM domain.
J.Mol.Biol., 400:145-154, 2010

PubMed Abstract: The nuclear protein cyclophilin 33 (Cyp33) is a peptidyl-prolyl cis-trans isomerase that catalyzes cis-trans isomerization of the peptide bond preceding a proline and promotes folding and conformational changes in folded and unfolded proteins. The N-terminal RNA-recognition motif (RRM) domain of Cyp33 has been found to associate with the third plant homeodomain (PHD3) finger of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly(A) RNA sequence. Here, we report a 1.9 A resolution crystal structure of the RRM domain of Cyp33 and describe the molecular mechanism of PHD3 and RNA recognition. The Cyp33 RRM domain folds into a five-stranded antiparallel beta-sheet and two alpha-helices. The RRM domain, but not the catalytic module of Cyp33, binds strongly to PHD3, exhibiting a 2 muM affinity as measured by isothermal titration calorimetry. NMR chemical shift perturbation (CSP) analysis and dynamics data reveal that the beta strands and the beta2-beta3 loop of the RRM domain are involved in the interaction with PHD3. Mutations in the PHD3-binding site or deletions in the beta2-beta3 loop lead to a significantly reduced affinity or abrogation of the interaction. The RNA-binding pocket of the Cyp33 RRM domain, mapped on the basis of NMR CSP and mutagenesis, partially overlaps with the PHD3-binding site, and RNA association is abolished in the presence of MLL PHD3. Full-length Cyp33 acts as a negative regulator of MLL-induced transcription and reduces the expression levels of MLL target genes MEIS1 and HOXA9. Together, these in vitro and in vivo data provide insight into the multiple functions of Cyp33 RRM and suggest a Cyp33-dependent mechanism for regulating the transcriptional activity of MLL.

PubMed: 20460131
DOI: 10.1016/j.jmb.2010.04.067

実験手法

X-RAY DIFFRACTION (1.85 Å)