Interactions between the intrinsically disordered regions of hnrnp-a2 and tdp-43 accelerate tdp-43s conformational transition

Wan Chin Chiang, Ming Hsuan Lee, Tsai Chen Chen, Jie Rong Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Most biological functions involve protein–protein interactions. Our understanding of these interactions is based mainly on those of structured proteins, because encounters between intrinsically disordered proteins (IDPs) or proteins with intrinsically disordered regions (IDRs) are much less studied, regardless of the fact that more than half eukaryotic proteins contain IDRs. RNA-binding proteins (RBPs) are a large family whose members almost all have IDRs in addition to RNA binding domains. These IDRs, having low sequence similarity, interact, but structural details on these interactions are still lacking. Here, using the IDRs of two RBPs (hnRNA-A2 and TDP-43) as a model, we demonstrate that the rate at which TDP-43s IDR undergoes the neurodegenerative disease related α-helix-to-β-sheet transition increases in relation to the amount of hnRNP-A2s IDR that is present. There are more than 1500 RBPs in human cells and most of them have IDRs. RBPs often join the same complexes to regulate genes. In addition to the structured RNA-recognition motifs, our study demonstrates a general mechanism through which RBPs may regulate each other’s functions through their IDRs.

Original languageEnglish
Article number5930
Pages (from-to)1-11
Number of pages11
JournalInternational Journal Of Molecular Sciences
Volume21
Issue number16
DOIs
StatePublished - 2 Aug 2020

Keywords

  • Intrinsically disordered protein
  • Liquid–liquid phase separation
  • Membraneless organelle
  • NMR spectroscopy

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