8AYG

Crystal structure of an intramolecular i-motif at the insulin-linked polymorphic region (ILPR)

8AYG の概要

• エントリーDOI: 10.2210/pdb8ayg/pdb
• 分子名称: Insulin-linked polymorphic region, ILPR DNA (31-MER) (2 entities in total)
• 機能のキーワード: i-motif, promoter, dna, insulin-linked polymorphic region
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18355.84

構造登録者

Parkinson, G.N.,Alexandrou, E.,Waller, Z.A.E.,El-Omari, K. (登録日: 2022-09-02, 公開日: 2023-09-13, 最終更新日: 2024-09-11)

主引用文献

Guneri, D.,Alexandrou, E.,El Omari, K.,Dvorakova, Z.,Chikhale, R.V.,Pike, D.T.S.,Waudby, C.A.,Morris, C.J.,Haider, S.,Parkinson, G.N.,Waller, Z.A.E.
Structural insights into i-motif DNA structures in sequences from the insulin-linked polymorphic region.
Nat Commun, 15:7119-7119, 2024

PubMed Abstract: The insulin-linked polymorphic region is a variable number of tandem repeats region of DNA in the promoter of the insulin gene that regulates transcription of insulin. This region is known to form the alternative DNA structures, i-motifs and G-quadruplexes. Individuals have different sequence variants of tandem repeats and although previous work investigated the effects of some variants on G-quadruplex formation, there is not a clear picture of the relationship between the sequence diversity, the DNA structures formed, and the functional effects on insulin gene expression. Here we show that different sequence variants of the insulin linked polymorphic region form different DNA structures in vitro. Additionally, reporter genes in cellulo indicate that insulin expression may change depending on which DNA structures form. We report the crystal structure and dynamics of an intramolecular i-motif, which reveal sequences within the loop regions forming additional stabilising interactions that are critical to formation of stable i-motif structures. The outcomes of this work reveal the detail in formation of stable i-motif DNA structures, with potential for rational based drug design for compounds to target i-motif DNA.

PubMed: 39164244
DOI: 10.1038/s41467-024-50553-0

実験手法

X-RAY DIFFRACTION (2.25 Å)