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

doi:10.1016/j.bbrc.2012.07.071

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

Department of Physics

Research output: Contribution to journal › Article › peer-review

120 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 language	English
Pages (from-to)	219-224
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	425
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2012.07.071
Publication status	Published - 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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10.1016/j.bbrc.2012.07.071

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@article{d314d8a491114d3b96f83c0979d89faf,

title = "The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity",

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.",

keywords = "DNA/RNA binding, N-terminus, Neurodegenerative disease, Oligomerization, TDP-43",

author = "Chang, \{Chung ke\} and Wu, \{Tzong Huah\} and Wu, \{Chu Ya\} and Chiang, \{Ming hui\} and Toh, \{Elsie Khai Woon\} and Hsu, \{Yin Chih\} and Lin, \{Ku Feng\} and Liao, \{Yu heng\} and Huang, \{Tai huang\} and Huang, \{Joseph Jen Tse\}",

note = "Funding Information: This work was supported by research grants from Academia Sinica and The National Science Council of the Republic of China (Grants NSC 97-2113-M-001-003-MY2, 98-2113-M-001-015-MY2, and NSC 100-2113-M-001-013-MY2 to J.J.H.; NSC100-2321-B-001-028 and NSC100-2311-B-001-023 to T.H.H.). T.-H.Y. was supported by Academia Sinica. We would like to thank Dr. Benjamin Tu and Dr. Hanna Yuan from Academia Sinica for providing full-length TDP-43, TDP 101{\textendash}191 , TDP 192{\textendash}265 and TDP 101{\textendash}265 plasmids. We also thank the mass spectrometry support from Dr. Mei-Chun Tseng and the suggestions of NMR experiments from Dr. Chi-fon Chang and Sunney I. Chan. NMR experiments were carried out with NMR spectrometers of the High-Field Nuclear Magnetic Resonance Center (HFNMRC) supported by National Research Program for Genomic Medicine, The National Science Council of the Republic of China. ",

year = "2012",

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doi = "10.1016/j.bbrc.2012.07.071",

language = "English",

volume = "425",

pages = "219--224",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

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T1 - The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity

AU - Chang, Chung ke

AU - Wu, Tzong Huah

AU - Wu, Chu Ya

AU - Chiang, Ming hui

AU - Toh, Elsie Khai Woon

AU - Hsu, Yin Chih

AU - Lin, Ku Feng

AU - Liao, Yu heng

AU - Huang, Tai huang

AU - Huang, Joseph Jen Tse

N1 - Funding Information: This work was supported by research grants from Academia Sinica and The National Science Council of the Republic of China (Grants NSC 97-2113-M-001-003-MY2, 98-2113-M-001-015-MY2, and NSC 100-2113-M-001-013-MY2 to J.J.H.; NSC100-2321-B-001-028 and NSC100-2311-B-001-023 to T.H.H.). T.-H.Y. was supported by Academia Sinica. We would like to thank Dr. Benjamin Tu and Dr. Hanna Yuan from Academia Sinica for providing full-length TDP-43, TDP 101–191 , TDP 192–265 and TDP 101–265 plasmids. We also thank the mass spectrometry support from Dr. Mei-Chun Tseng and the suggestions of NMR experiments from Dr. Chi-fon Chang and Sunney I. Chan. NMR experiments were carried out with NMR spectrometers of the High-Field Nuclear Magnetic Resonance Center (HFNMRC) supported by National Research Program for Genomic Medicine, The National Science Council of the Republic of China.

PY - 2012/8/24

Y1 - 2012/8/24

N2 - 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.

AB - 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.

KW - DNA/RNA binding

KW - N-terminus

KW - Neurodegenerative disease

KW - Oligomerization

KW - TDP-43

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UR - https://www.scopus.com/pages/publications/84865386915#tab=citedBy

U2 - 10.1016/j.bbrc.2012.07.071

DO - 10.1016/j.bbrc.2012.07.071

M3 - Article

C2 - 22835933

AN - SCOPUS:84865386915

SN - 0006-291X

VL - 425

SP - 219

EP - 224

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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