dc.contributor.author |
Zanotti, KJ |
en |
dc.contributor.author |
Lackey, PE |
en |
dc.contributor.author |
Evans, Genevieve |
en |
dc.contributor.author |
Mihailescu, MR |
en |
dc.date.accessioned |
2011-09-07T01:23:18Z |
en |
dc.date.issued |
2006-07-11 |
en |
dc.identifier.citation |
BIOCHEMISTRY-US 45(27):8319-8330 11 Jul 2006 |
en |
dc.identifier.issn |
0006-2960 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/7844 |
en |
dc.description.abstract |
Fragile X syndrome, the most common form of inherited mental retardation, is the result of an unstable expansion of a CGG trinucleotide repeat in the 5′ UTR of the fragile X mental retardation-1 (FMR1) gene. The abnormal hypermethylation of the expanded CGG repeats causes the transcriptional silencing of the FMR1 gene and, consequently, the loss of the fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein that binds to G quartet forming RNA using its RGG box motif. In this study we have performed a thermodynamic analysis of the interactions between the FMRP RGG box domain and Sc1, an RNA molecule which had been previously shown to be bound with high affinity by both the full-length FMRP and by its RGG box domain. We have determined that the association between the FMRP RGG box and Sc1 RNA is dominated by hydrophobic and hydrogen bond interactions, with minor contributions from electrostatic interactions, and that the FMRP RGG box binding increases the stability of the G quartet RNA structure significantly. Interestingly, we found that the G quartet recognition is necessary but not sufficient for the FMRP RGG box binding to this RNA target, indicating that additional interactions of the peptide, possibly with the stem and/or stem-G quartet junction region, are required. Our results also indicate that the G quartet RNA recognition is not a general feature of the RGG box motif but rather carries some sequence, protein and/or RNA, specificity. |
en |
dc.language |
EN |
en |
dc.publisher |
AMER CHEMICAL SOC |
en |
dc.relation.ispartofseries |
BIOCHEMISTRY-US |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0006-2960/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
MESSENGER-RNAS |
en |
dc.subject |
CRYSTAL-STRUCTURE |
en |
dc.subject |
IN-VIVO |
en |
dc.subject |
BINDING |
en |
dc.subject |
FMRP |
en |
dc.subject |
DOMAIN |
en |
dc.subject |
IDENTIFICATION |
en |
dc.subject |
POLYRIBOSOMES |
en |
dc.subject |
PEPTIDE |
en |
dc.subject |
GENE |
en |
dc.title |
Thermodynamics of the fragile X mental retardation protein RGG box interactions with G quartet forming RNA |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/bi060209a |
en |
pubs.issue |
27 |
en |
pubs.begin-page |
8319 |
en |
pubs.volume |
45 |
en |
dc.rights.holder |
Copyright: 2006 American Chemical Society |
en |
dc.identifier.pmid |
16819831 |
en |
pubs.end-page |
8330 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
188842 |
en |
pubs.record-created-at-source-date |
2011-10-18 |
en |
pubs.dimensions-id |
16819831 |
en |