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

Research output: Contribution to journalArticle

41 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

Fingerprint Dive into the research topics of 'The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity'. Together they form a unique fingerprint.

  • Cite this

    Chang, C. K., Wu, T. H., Wu, C. Y., Chiang, M. H., Toh, E. K. W., Hsu, Y. C., Lin, K. F., Liao, Y. H., Huang, T. H., & Huang, J. J. T. (2012). The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity. Biochemical and Biophysical Research Communications, 425(2), 219-224. https://doi.org/10.1016/j.bbrc.2012.07.071