6V0N

PRMT5 bound to PBM peptide from Riok1

6V0N の概要

• エントリーDOI: 10.2210/pdb6v0n/pdb
• 分子名称: Protein arginine N-methyltransferase 5, Methylosome protein 50, Riok1 PBM peptide, ... (5 entities in total)
• 機能のキーワード: methylation, epigenetics, splicing, sdma, transferase-splicing complex, transferase/splicing
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 111222.55

構造登録者

McMIllan, B.J.,Raymond, D.D. (登録日: 2019-11-19, 公開日: 2020-08-26, 最終更新日: 2023-10-11)

主引用文献

Mulvaney, K.M.,Blomquist, C.,Acharya, N.,Li, R.,Ranaghan, M.J.,O'Keefe, M.,Rodriguez, D.J.,Young, M.J.,Kesar, D.,Pal, D.,Stokes, M.,Nelson, A.J.,Jain, S.S.,Yang, A.,Mullin-Bernstein, Z.,Columbus, J.,Bozal, F.K.,Skepner, A.,Raymond, D.,LaRussa, S.,McKinney, D.C.,Freyzon, Y.,Baidi, Y.,Porter, D.,Aguirre, A.J.,Ianari, A.,McMillan, B.,Sellers, W.R.
Molecular basis for substrate recruitment to the PRMT5 methylosome.
Mol.Cell, 81:3481-, 2021

PubMed Abstract: PRMT5 is an essential arginine methyltransferase and a therapeutic target in MTAP-null cancers. PRMT5 uses adaptor proteins for substrate recruitment through a previously undefined mechanism. Here, we identify an evolutionarily conserved peptide sequence shared among the three known substrate adaptors (CLNS1A, RIOK1, and COPR5) and show that it is necessary and sufficient for interaction with PRMT5. We demonstrate that PRMT5 uses modular adaptor proteins containing a common binding motif for substrate recruitment, comparable with other enzyme classes such as kinases and E3 ligases. We structurally resolve the interface with PRMT5 and show via genetic perturbation that it is required for methylation of adaptor-recruited substrates including the spliceosome, histones, and ribosomal complexes. Furthermore, disruption of this site affects Sm spliceosome activity, leading to intron retention. Genetic disruption of the PRMT5-substrate adaptor interface impairs growth of MTAP-null tumor cells and is thus a site for development of therapeutic inhibitors of PRMT5.

PubMed: 34358446
DOI: 10.1016/j.molcel.2021.07.019

実験手法

X-RAY DIFFRACTION (2.11 Å)