8CXF

Crystal structure of an i-motif from the HRAS promoter region

Summary for 8CXF

• Entry DOI: 10.2210/pdb8cxf/pdb
• Descriptor: HRAS DNA, 1-METHOXY-2-[2-(2-METHOXY-ETHOXY]-ETHANE (3 entities in total)
• Functional Keywords: hras, i-motif, dna
• Biological source: Homo sapiens
• Total number of polymer chains: 2
• Total formula weight: 16626.45

Authors

Yatsunyk, L.A.,Li, K.S. (deposition date: 2022-05-20, release date: 2023-05-10, Last modification date: 2024-05-22)

Primary citation

Li, K.S.,Jordan, D.,Lin, L.Y.,McCarthy, S.E.,Schneekloth Jr., J.S.,Yatsunyk, L.A.
Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.
Angew.Chem.Int.Ed.Engl., 62:e202301666-e202301666, 2023

PubMed Abstract: An i-motif is a non-canonical DNA structure implicated in gene regulation and linked to cancers. The C-rich strand of the HRAS oncogene, 5'-CGCCCGTGCCCTGCGCCCGCAACCCGA-3' (herein referred to as iHRAS), forms an i-motif in vitro but its exact structure was unknown. HRAS is a member of the RAS proto-oncogene family. About 19 % of US cancer patients carry mutations in RAS genes. We solved the structure of iHRAS at 1.77 Å resolution. The structure reveals that iHRAS folds into a double hairpin. The two double hairpins associate in an antiparallel fashion, forming an i-motif dimer capped by two loops on each end and linked by a connecting region. Six C-C base pairs form each i-motif core, and the core regions are extended by a G-G base pair and a cytosine stacking. Extensive canonical and non-canonical base pairing and stacking stabilizes the connecting region and loops. The iHRAS structure is the first atomic resolution structure of an i-motif from a human oncogene. This structure sheds light on i-motifs folding and function in the cell.

PubMed: 36995904
DOI: 10.1002/anie.202301666

Experimental method

X-RAY DIFFRACTION (1.77 Å)