6ROL

Structure of IMP2 KH34 domains

6ROL の概要

• エントリーDOI: 10.2210/pdb6rol/pdb
• 分子名称: Insulin-like growth factor 2 mRNA-binding protein 2, GLYCEROL, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• 機能のキーワード: specificity, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 75902.36

構造登録者

Bhaskar, V.,Biswas, J.,Singer, R.H.,Chao, J.A. (登録日: 2019-05-13, 公開日: 2019-10-16, 最終更新日: 2024-01-24)

主引用文献

Biswas, J.,Patel, V.L.,Bhaskar, V.,Chao, J.A.,Singer, R.H.,Eliscovich, C.
The structural basis for RNA selectivity by the IMP family of RNA-binding proteins.
Nat Commun, 10:4440-4440, 2019

PubMed Abstract: The IGF2 mRNA-binding proteins (ZBP1/IMP1, IMP2, IMP3) are highly conserved post-transcriptional regulators of RNA stability, localization and translation. They play important roles in cell migration, neural development, metabolism and cancer cell survival. The knockout phenotypes of individual IMP proteins suggest that each family member regulates a unique pool of RNAs, yet evidence and an underlying mechanism for this is lacking. Here, we combine systematic evolution of ligands by exponential enrichment (SELEX) and NMR spectroscopy to demonstrate that the major RNA-binding domains of the two most distantly related IMPs (ZBP1 and IMP2) bind to different consensus sequences and regulate targets consistent with their knockout phenotypes and roles in disease. We find that the targeting specificity of each IMP is determined by few amino acids in their variable loops. As variable loops often differ amongst KH domain paralogs, we hypothesize that this is a general mechanism for evolving specificity and regulation of the transcriptome.

PubMed: 31570709
DOI: 10.1038/s41467-019-12193-7

実験手法

X-RAY DIFFRACTION (2.1 Å)