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Crystal structure of parallel G-quadruplex formed by the two-repeat ALS- and FTD-related GGGGCC sequence.
Geng, Yanyan; Liu, Changdong; Cai, Qixu; Luo, Zhipu; Miao, Haitao; Shi, Xiao; Xu, Naining; Fung, Chun Po; Choy, To To; Yan, Bing; Li, Ning; Qian, Peiyuan; Zhou, Bo; Zhu, Guang.
Afiliación
  • Geng Y; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Liu C; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Cai Q; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Luo Z; Institute of Molecular Enzymology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu, 215123, China.
  • Miao H; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Shi X; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Xu N; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Fung CP; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Choy TT; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Yan B; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Li N; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Qian P; Hong Kong Branch of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Zhou B; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
  • Zhu G; Institute for Advanced Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, 00000, China.
Nucleic Acids Res ; 49(10): 5881-5890, 2021 06 04.
Article en En | MEDLINE | ID: mdl-34048588
The hexanucleotide repeat expansion, GGGGCC (G4C2), within the first intron of the C9orf72 gene is known to be the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The G4C2 repeat expansions, either DNA or RNA, are able to form G-quadruplexes which induce toxicity leading to ALS/FTD. Herein, we report a novel crystal structure of d(G4C2)2 that self-associates to form an eight-layer parallel tetrameric G-quadruplex. Two d(G4C2)2 associate together as a parallel dimeric G-quadruplex which folds into a tetramer via 5'-to-5' arrangements. Each dimer consists of four G-tetrads connected by two CC propeller loops. Especially, the 3'-end cytosines protrude out and form C·C+•C·C+/ C·C•C·C+ quadruple base pair or C•C·C+ triple base pair stacking on the dimeric block. Our work sheds light on the G-quadruplexes adopted by d(G4C2) and yields the invaluable structural details for the development of small molecules to tackle neurodegenerative diseases, ALS and FTD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Secuencias Repetitivas de Ácidos Nucleicos / Expansión de las Repeticiones de ADN / G-Cuádruplex / Demencia Frontotemporal / Proteína C9orf72 / Esclerosis Amiotrófica Lateral Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Secuencias Repetitivas de Ácidos Nucleicos / Expansión de las Repeticiones de ADN / G-Cuádruplex / Demencia Frontotemporal / Proteína C9orf72 / Esclerosis Amiotrófica Lateral Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido