Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Biochemical and biophysical research communications, 2012-08, Vol.425 (2), p.219-224

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

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