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.
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
authors: Chung-ke
authors: CK
authors: Chang
authors: Tzong-Huah
authors: TH
authors: Wu
authors: Chu-Ya
authors: CY
authors: Wu
authors: Ming-hui
authors: MH
authors: Chiang
authors: Elsie Khai-Woon
authors: EK
authors: Toh
authors: Yin-Chih
authors: YC
authors: Hsu
authors: Ku-Feng
authors: KF
authors: Lin
authors: Yu-heng
authors: YH
authors: Liao
authors: Tai-huang
authors: TH
authors: Huang
authors: Joseph Jen-Tse
authors: JJ
authors: Huang
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017510:Protein Folding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA