Crystal Structure Of An i-Motif From The HRAS Oncogene Promoter
Document Type
Article
Publication Date
6-26-2023
Published In
Angewandte Chemie International Edition
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.
Keywords
Dimers, Gene Regulation, Non-Canonical Base Pairing, X-Ray Crystallography, i-Motifs
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Kevin S. Li , '22; Deondre Jordan , '19; Linda Y. Lin , '20; Sawyer E. McCarthy; J. S. Schneekloth Jr.; and Liliya A. Yatsunyk.
(2023).
"Crystal Structure Of An i-Motif From The HRAS Oncogene Promoter".
Angewandte Chemie International Edition.
Volume 62,
Issue 26.
DOI: 10.1002/anie.202301666
https://works.swarthmore.edu/fac-chemistry/287