5M8I

Solution structure of CUG-BP2 RRM3 in complex with 5'-UUUAA-3' RNA

5M8I の概要

• エントリーDOI: 10.2210/pdb5m8i/pdb
• NMR情報: BMRB: 34057
• 分子名称: CUGBP Elav-like family member 2, RNA (5'-R(*UP*UP*UP*AP*A)-3') (2 entities in total)
• 機能のキーワード: rna binding protein, rna, rna recognition motif
• 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: 14374.63

構造登録者

Diarra dit Konte, N.,Damberger, F.F.,Allain, F.H.T. (登録日: 2016-10-28, 公開日: 2017-10-11, 最終更新日: 2024-06-19)

主引用文献

Diarra Dit Konte, N.,Krepl, M.,Damberger, F.F.,Ripin, N.,Duss, O.,Sponer, J.,Allain, F.H.
Aromatic side-chain conformational switch on the surface of the RNA Recognition Motif enables RNA discrimination.
Nat Commun, 8:654-654, 2017

PubMed Abstract: The cyclooxygenase-2 is a pro-inflammatory and cancer marker, whose mRNA stability and translation is regulated by the CUG-binding protein 2 interacting with AU-rich sequences in the 3' untranslated region. Here, we present the solution NMR structure of CUG-binding protein 2 RRM3 in complex with 5'-UUUAA-3' originating from the COX-2 3'-UTR. We show that RRM3 uses the same binding surface and protein moieties to interact with AU- and UG-rich RNA motifs, binding with low and high affinity, respectively. Using NMR spectroscopy, isothermal titration calorimetry and molecular dynamics simulations, we demonstrate that distinct sub-states characterized by different aromatic side-chain conformations at the RNA-binding surface allow for high- or low-affinity binding with functional implications. This study highlights a mechanism for RNA discrimination possibly common to multiple RRMs as several prominent members display a similar rearrangement of aromatic residues upon binding their targets.The RNA Recognition Motif (RRM) is the most ubiquitous RNA binding domain. Here the authors combined NMR and molecular dynamics simulations and show that the RRM RNA binding surface exists in different states and that a conformational switch of aromatic side-chains fine-tunes sequence specific binding affinities.

PubMed: 28935965
DOI: 10.1038/s41467-017-00631-3

実験手法

SOLUTION NMR