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Nat Struct Mol Biol. 2011 Jun 05;18(7):796-804. doi: 10.1038/nsmb.2064.

Structure-function studies of FMRP RGG peptide recognition of an RNA duplex-quadruplex junction.

Nature structural & molecular biology

Anh Tuân Phan, Vitaly Kuryavyi, Jennifer C Darnell, Alexander Serganov, Ananya Majumdar, Serge Ilin, Tanya Raslin, Anna Polonskaia, Cynthia Chen, David Clain, Robert B Darnell, Dinshaw J Patel

Affiliations

  1. Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. [email protected]

PMID: 21642970 PMCID: PMC3130835 DOI: 10.1038/nsmb.2064

Abstract

We have determined the solution structure of the complex between an arginine-glycine-rich RGG peptide from the human fragile X mental retardation protein (FMRP) and an in vitro-selected guanine-rich (G-rich) sc1 RNA. The bound RNA forms a newly discovered G-quadruplex separated from the flanking duplex stem by a mixed junctional tetrad. The RGG peptide is positioned along the major groove of the RNA duplex, with the G-quadruplex forcing a sharp turn of R(10)GGGGR(15) at the duplex-quadruplex junction. Arg10 and Arg15 form cross-strand specificity-determining intermolecular hydrogen bonds with the major-groove edges of guanines of adjacent Watson-Crick G•C pairs. Filter-binding assays on RNA and peptide mutations identify and validate contributions of peptide-RNA intermolecular contacts and shape complementarity to molecular recognition. These findings on FMRP RGG domain recognition by a combination of G-quadruplex and surrounding RNA sequences have implications for the recognition of other genomic G-rich RNAs.

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