6G99

Solution structure of FUS-ZnF bound to UGGUG

6G99 の概要

• エントリーDOI: 10.2210/pdb6g99/pdb
• NMR情報: BMRB: 34258
• 分子名称: RNA-binding protein FUS, RNA (5'-R(*UP*GP*GP*UP*G)-3'), ZINC ION (3 entities in total)
• 機能のキーワード: rna zinc finger rna binding protein zinc ribbon, rna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 6196.41

構造登録者

Loughlin, F.E.,Allain, F.H.-T. (登録日: 2018-04-10, 公開日: 2019-02-20, 最終更新日: 2024-05-15)

主引用文献

Loughlin, F.E.,Lukavsky, P.J.,Kazeeva, T.,Reber, S.,Hock, E.M.,Colombo, M.,Von Schroetter, C.,Pauli, P.,Clery, A.,Muhlemann, O.,Polymenidou, M.,Ruepp, M.D.,Allain, F.H.
The Solution Structure of FUS Bound to RNA Reveals a Bipartite Mode of RNA Recognition with Both Sequence and Shape Specificity.
Mol. Cell, 73:490-504.e6, 2019

PubMed Abstract: Fused in sarcoma (FUS) is an RNA binding protein involved in regulating many aspects of RNA processing and linked to several neurodegenerative diseases. Transcriptomics studies indicate that FUS binds a large variety of RNA motifs, suggesting that FUS RNA binding might be quite complex. Here, we present solution structures of FUS zinc finger (ZnF) and RNA recognition motif (RRM) domains bound to RNA. These structures show a bipartite binding mode of FUS comprising of sequence-specific recognition of a NGGU motif via the ZnF and an unusual shape recognition of a stem-loop RNA via the RRM. In addition, sequence-independent interactions via the RGG repeats significantly increase binding affinity and promote destabilization of structured RNA conformation, enabling additional binding. We further show that disruption of the RRM and ZnF domains abolishes FUS function in splicing. Altogether, our results rationalize why deciphering the RNA binding mode of FUS has been so challenging.

PubMed: 30581145
DOI: 10.1016/j.molcel.2018.11.012

実験手法

SOLUTION NMR