4G56

Crystal Structure of full length PRMT5/MEP50 complexes from Xenopus laevis

4G56 の概要

• エントリーDOI: 10.2210/pdb4g56/pdb
• 分子名称: Hsl7 protein, MGC81050 protein, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• 機能のキーワード: protein arginine methyltransferase, protein complexes, histone methylation, transferase, structural genomics, psi-biology, new york structural genomics research consortium, nysgrc
• 由来する生物種: Xenopus laevis (clawed frog,common platanna,platanna); 詳細
• 細胞内の位置: Cytoplasm: Q6NUA1 Q6NUD0
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 229941.22

構造登録者

Ho, M.,Wilczek, C.,Bonanno, J.,Shechter, D.,Almo, S.C.,New York Structural Genomics Research Consortium (NYSGRC) (登録日: 2012-07-17, 公開日: 2012-10-03, 最終更新日: 2024-10-30)

主引用文献

Ho, M.C.,Wilczek, C.,Bonanno, J.B.,Xing, L.,Seznec, J.,Matsui, T.,Carter, L.G.,Onikubo, T.,Kumar, P.R.,Chan, M.K.,Brenowitz, M.,Cheng, R.H.,Reimer, U.,Almo, S.C.,Shechter, D.
Structure of the arginine methyltransferase PRMT5-MEP50 reveals a mechanism for substrate specificity
Plos One, 8:e57008-e57008, 2013

PubMed Abstract: The arginine methyltransferase PRMT5-MEP50 is required for embryogenesis and is misregulated in many cancers. PRMT5 targets a wide variety of substrates, including histone proteins involved in specifying an epigenetic code. However, the mechanism by which PRMT5 utilizes MEP50 to discriminate substrates and to specifically methylate target arginines is unclear. To test a model in which MEP50 is critical for substrate recognition and orientation, we determined the crystal structure of Xenopus laevis PRMT5-MEP50 complexed with S-adenosylhomocysteine (SAH). PRMT5-MEP50 forms an unusual tetramer of heterodimers with substantial surface negative charge. MEP50 is required for PRMT5-catalyzed histone H2A and H4 methyltransferase activity and binds substrates independently. The PRMT5 catalytic site is oriented towards the cross-dimer paired MEP50. Histone peptide arrays and solution assays demonstrate that PRMT5-MEP50 activity is inhibited by substrate phosphorylation and enhanced by substrate acetylation. Electron microscopy and reconstruction showed substrate centered on MEP50. These data support a mechanism in which MEP50 binds substrate and stimulates PRMT5 activity modulated by substrate post-translational modifications.

PubMed: 23451136
DOI: 10.1371/journal.pone.0057008

実験手法

X-RAY DIFFRACTION (2.95 Å)