6QEY

IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties

6QEY の概要

• エントリーDOI: 10.2210/pdb6qey/pdb
• 分子名称: Insulin-like growth factor 2 mRNA-binding protein 1, ACETONITRILE, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: kh domains, imp1, rna-binding, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19937.75

構造登録者

Dagil, R.,Ball, N.J.,Ogrodowicz, R.W.,Purkiss, A.G.,Taylor, I.A.,Ramos, A. (登録日: 2019-01-09, 公開日: 2019-03-27, 最終更新日: 2024-05-15)

主引用文献

Dagil, R.,Ball, N.J.,Ogrodowicz, R.W.,Hobor, F.,Purkiss, A.G.,Kelly, G.,Martin, S.R.,Taylor, I.A.,Ramos, A.
IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties.
Nucleic Acids Res., 47:4334-4348, 2019

PubMed Abstract: IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-binding domains. Here, we dissect the structure and RNA-binding properties of two key RNA-binding domains of IMP1, KH1 and KH2, and we build a kinetic model for the recognition of RNA targets. Our data and model explain how the two domains are organized as an intermolecular pseudo-dimer and that the important role they play in mRNA target recognition is underpinned by the high RNA-binding affinity and fast kinetics of this KH1KH2-RNA recognition unit. Importantly, the high-affinity RNA-binding by KH1KH2 is achieved by an inter-domain coupling 50-fold stronger than that existing in a second pseudo-dimer in the protein, KH3KH4. The presence of this strong coupling supports a role of RNA re-modelling in IMP1 recognition of known cancer targets.

PubMed: 30864660
DOI: 10.1093/nar/gkz136

実験手法

X-RAY DIFFRACTION (2.2 Å)