Two G-quadruplex structures adopted by oligonucleotide model of ALS and FTD linked GGGGCC repeats
published: July 21, 2017, recorded: May 2017, views: 804
Slides
Related content
Report a problem or upload files
If 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.
Description
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.
Link this page
Would you like to put a link to this lecture on your homepage?Go ahead! Copy the HTML snippet !
Write your own review or comment: