RNA architecture dictates the conformations of a bound peptide

Abstract

Our structural studies establish that RNA architecture dictates whether the same HIV-1 Rev peptide folds into an extended or alpha-helical conformation on complex formation. Arginine-rich peptides can therefore adapt distinct secondary folds to complement the tertiary folds of their RNA targets. This contrasts with protein-RNA complexes in which elements of RNA secondary structure adapt to fit within the tertiary folds of their protein targets.

Structure determination and dynamics of protein–RNA complexes by NMR spectroscopy

“…Alternatively, the affinity purification tag can be separated from the protein of interest. In the case of small peptides, removal of the affinity purification tag was often achieved using cyanogen bromide that specifically hydrolyzes peptide bonds C-terminal of methionines [7,9,15,16,19,33,42,44]. In the case of protein domains that often contain internal methionines, other methods for cleavage are generally used and involve specific proteases.…”

“…The samples and methodologies for peptide-RNA complexes are almost identical to those for protein-RNA complexes with the exception that peptides are often chemically synthesized [7,8,11,19,23,31,[41][42][43][44]. This offers the possibility to introduce site-specific isotope labeling at a certain residue.…”

“…For example single 15 N [Gly] labels were introduced into a 14-residue peptide to facilitate the assignments of three glycine residues [31]. However, bacterial expression is also frequently used to generate uniform 15 N or 15 N/ 13 C labeled peptides [6,7,9,19,33,42,44,165].…”

“…Indeed, 19 out of 22 structures of viral protein-RNA complexes were solved by NMR [4, 6, 8, 10-13, 16, 19, 23, 31, 41-45]. Three types of viral protein-RNA complexes were studied: the complexes between the viral protein Rev and its RNA target, the RRE, involved in RNA export [6,16,19,41,42,44] ; the complexes between the viral protein Tat (trans-activator) protein and its RNA target, the TAR (Trans-Activator Response element), involved in transcription regulation [8,11,23,31,43] ; the complexes between the viral protein NC and its RNA target, the Ψ-site, involved in RNA packaging [4,10,12,13,45].…”

Aptamer-based therapeutics and their potential in radiopharmaceutical design

“…This is simply based on the ability of nucleotide bases to interact with each other through canonical Watson-Crick as well as unusual base pairing. The existence of oligonucleotide sequences that could assume a myriad of shapes within a random sequence library is the basis for the remarkable success of generating aptamers to a wide variety of target molecules (Lin and Patel, 1996;Patel and Suri, 2000;Patel et al, 1997;Ye et al, 1999). RNA has intrinsic properties that lead to the formation of a variety of elaborate structures, some of which are able to catalyse reactions and others are able to function as receptors and ligands.…”