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

97 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 101–191 , 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. ",

year = "2012",

month = aug,

day = "24",

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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TY - JOUR

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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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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