6HPJ

Structure of human SRSF1 RRM1 bound to AACAAA RNA

6HPJ の概要

• エントリーDOI: 10.2210/pdb6hpj/pdb
• NMR情報: BMRB: 34317
• 分子名称: Immunoglobulin G-binding protein G,Serine/arginine-rich splicing factor 1, RNA (5'-R(*AP*AP*CP*AP*AP*A)-3') (2 entities in total)
• 機能のキーワード: splicing, sr protein, srsf1, rrm, spinal muscular atrophy, sma, rna, rna binding protein
• 由来する生物種: Streptococcus sp. group G; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19862.95

構造登録者

Allain, F.T.H.,Clery, A. (登録日: 2018-09-21, 公開日: 2020-11-18, 最終更新日: 2024-05-15)

主引用文献

Clery, A.,Krepl, M.,Nguyen, C.K.X.,Moursy, A.,Jorjani, H.,Katsantoni, M.,Okoniewski, M.,Mittal, N.,Zavolan, M.,Sponer, J.,Allain, F.H.
Structure of SRSF1 RRM1 bound to RNA reveals an unexpected bimodal mode of interaction and explains its involvement in SMN1 exon7 splicing.
Nat Commun, 12:428-428, 2021

PubMed Abstract: The human prototypical SR protein SRSF1 is an oncoprotein that contains two RRMs and plays a pivotal role in RNA metabolism. We determined the structure of the RRM1 bound to RNA and found that the domain binds preferentially to a CN motif (N is for any nucleotide). Based on this solution structure, we engineered a protein containing a single glutamate to asparagine mutation (E87N), which gains the ability to bind to uridines and thereby activates SMN exon7 inclusion, a strategy that is used to cure spinal muscular atrophy. Finally, we revealed that the flexible inter-RRM linker of SRSF1 allows RRM1 to bind RNA on both sides of RRM2 binding site. Besides revealing an unexpected bimodal mode of interaction of SRSF1 with RNA, which will be of interest to design new therapeutic strategies, this study brings a new perspective on the mode of action of SRSF1 in cells.

PubMed: 33462199
DOI: 10.1038/s41467-020-20481-w

実験手法

SOLUTION NMR