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

Journal Article · Fri Aug 24 04:00:00 EDT 2012 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2012.07.071· OSTI ID:22210200

Chang, Chung-ke ^[1]; Wu, Tzong-Huah ^[2]; Wu, Chu-Ya ^[2]; Chiang, Ming-hui; Toh, Elsie Khai-Woon ^[1]; Hsu, Yin-Chih; Lin, Ku-Feng ^[2]; Liao, Yu-heng ^[1]; Huang, Tai-huang ^[1]

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1. Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China)
2. Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China)

Highlights: Black-Right-Pointing-Pointer The N-terminus of TDP-43 contains an independently folded structural domain (NTD). Black-Right-Pointing-Pointer The structural domains of TDP-43 are arranged in a beads-on-a-string fashion. Black-Right-Pointing-Pointer The NTD promotes TDP-43 oligomerization in a concentration-dependent manner. Black-Right-Pointing-Pointer The NTD may assist nucleic acid-binding activity of TDP-43. -- 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.

• OSTI ID: 22210200
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 425; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ABUNDANCE
ANISOTROPY
CONCENTRATION RATIO
DICHROISM
DNA
FLUORESCENCE
NERVOUS SYSTEM DISEASES
NUCLEAR MAGNETIC RESONANCE
RNA