Two G-quadruplex structures adopted by oligonucleotide model of ALS and FTD linked GGGGCC repeats
published: July 21, 2017, recorded: May 2017, views: 8
Report a problem or upload filesIf you have found a problem with this lecture or would like to send us extra material, articles, exercises, etc., please use our ticket system to describe your request and upload the data.
Enter your e-mail into the 'Cc' field, and we will keep you updated with your request's status.
The most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a large increase in the number of GGGGCC repeats located within the non-coding region of C9orf72 gene. Non-canonical structures adopted by expanded GGGGCC repeats, including G-quadruplexes, have been proposed to be crucial in pathogenesis. G-rich oligonucleotides can form in the presence of K+ or Na+ ions non-canonical four-stranded structures called G-quadruplexes, composed of stacked layers of G-quartets that are formed by four guanine residues connected by Hoogsteen hydrogen bonds. G-quadruplexes are known to be structurally diverse and their folding sensitive to oligonucleotide sequence and experimental conditions. In addition, several G-quadruplex structures often coexist in solution, representing a great challenge for high-resolution structure determination. Oligonucleotide d[(G4C2)3G4], chosen as the shortest model with the ability to fold intra-molecularly, formed two major and several minor G-quadruplex structures. Structural polymorphism was reduced by dG to 8Br-dG substitution and led to stabilization of two structures in d[(G4C2)3GGBrGG]. Interestingly, relative populations of G-quadruplex structures were sensitive to pH and rate of cooling when folding from thermally denatured state in the presence of K+ ions. Two different folding conditions were established that selectively favor formation of mostly one of the structures, thus facilitating their individual structural characterization with NMR. Two G-quadruplex structures are topologically very similar, however, they exhibit unique structures and distinct dynamic properties.
Download slides: encals2017_brcic_structures_adopted_01.pdf (12.9 MB)
Link this pageWould you like to put a link to this lecture on your homepage?
Go ahead! Copy the HTML snippet !