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

33 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

Fingerprint

Frontotemporal Lobar Degeneration
Oligomerization
Neurodegenerative diseases
Fluorescence Polarization
RNA-Binding Proteins
DNA
Amyotrophic Lateral Sclerosis
DNA-Binding Proteins
Circular Dichroism
Neurodegenerative Diseases
Structural properties
Anisotropy
Magnetic Resonance Spectroscopy
Physical properties
Fluorescence
Nuclear magnetic resonance

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chang, C. K., Wu, T. H., Wu, C. Y., Chiang, M. H., Toh, E. K. W., Hsu, Y. C., ... 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

The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity. / Chang, Chung ke; Wu, Tzong Huah; Wu, Chu Ya; Chiang, Ming hui; Toh, Elsie Khai Woon; Hsu, Yin Chih; Lin, Ku Feng; Liao, Yu heng; Huang, Tai-huang; Huang, Joseph Jen Tse.

In: Biochemical and Biophysical Research Communications, Vol. 425, No. 2, 24.08.2012, p. 219-224.

Research output: Contribution to journalArticle

Chang, CK, Wu, TH, Wu, CY, Chiang, MH, Toh, EKW, Hsu, YC, Lin, KF, Liao, YH, Huang, T & Huang, JJT 2012, 'The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity', Biochemical and Biophysical Research Communications, vol. 425, no. 2, pp. 219-224. https://doi.org/10.1016/j.bbrc.2012.07.071
Chang, Chung ke ; Wu, Tzong Huah ; Wu, Chu Ya ; Chiang, Ming hui ; Toh, Elsie Khai Woon ; Hsu, Yin Chih ; Lin, Ku Feng ; Liao, Yu heng ; Huang, Tai-huang ; Huang, Joseph Jen Tse. / The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 425, No. 2. pp. 219-224.
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