The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity

  • Chung ke Chang
  • , Tzong Huah Wu
  • , Chu Ya Wu
  • , Ming hui Chiang
  • , Elsie Khai Woon Toh
  • , Yin Chih Hsu
  • , Ku Feng Lin
  • , Yu heng Liao
  • , Tai huang Huang*
  • , Joseph Jen Tse Huang
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

Abstract

TDP-43 is a DNA/RNA-binding protein associated with different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U). Here, the structural and physical properties of the N-terminus on TDP-43 have been carefully characterized through a combination of nuclear magnetic resonance (NMR), circular dichroism (CD) and fluorescence anisotropy studies. We demonstrate for the first time the importance of the N-terminus in promoting TDP-43 oligomerization and enhancing its DNA-binding affinity. An unidentified structural domain in the N-terminus is also disclosed. Our findings provide insights into the N-terminal domain function of TDP-43.

Original languageEnglish
Pages (from-to)219-224
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume425
Issue number2
DOIs
Publication statusPublished - 2012 Aug 24

Keywords

  • DNA/RNA binding
  • N-terminus
  • Neurodegenerative disease
  • Oligomerization
  • TDP-43

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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