Sequence and structure space of RNA‐binding peptides

Abstract

Studies of RNA-binding peptides, and recent combinatorial library experiments in particular, have demonstrated that diverse peptide sequences and structures can be used to recognize specific RNA sites. The identification of large numbers of sequences capable of binding to a particular site has provided extensive phylogenetic information used to deduce basic principles of recognition. The high frequency at which RNA-binding peptides are found in large sequence libraries suggests plausible routes to evolve sequence-specific binders, facilitating the design of new binding molecules and perhaps reflecting characteristics of natural evolution.

Arginine-rich motifs present multiple interfaces for specific binding by RNA

“…The wealth of arginine residues allows multiple interactions to potentially be formed, and peptide and RNA structural flexibility allows a subset of productive interfaces to be realized. Although structural work has hinted at this before (for reviews, see Frankel 2000;Das and Frankel 2003), we now show systematically that ARMs are versatile binding domains, able to bind diverse RNA molecules via different mechanisms. Overall, the ARM appears to be a much more adaptable and flexible RNA binding element than other RNA binding domains.…”

Water, Shape Recognition, Salt Bridges, and Cation–Pi Interactions Differentiate Peptide Recognition of the HIV Rev-Responsive Element

“…Among the many classes of RNA-binding motifs, arginine-rich motifs (ARMs) 1 are particularly interesting as they are relatively short in length, have little sequence similarity aside from containing many arginine residues, and exhibit diverse structures. [2][3][4][5] For example, in bovine immunodeficiency virus Tat, human immunodeficiency virus (HIV) Rev, bacteriophage λ N, HIV Tat, and human T cell leukemia virus type 1 Rex peptides, the RNA-binding peptides adopt a variety of different structures upon association with the RNA target, 6,7 including a β-hairpin, 8 an α-helix, 9,10 a distorted α-helix, 11 an extended conformation, 12 and an S-shaped conformation, 13 respectively.…”

Evolvability of the mode of peptide binding by an RNA

“…The arginine-rich RNA-binding motif is a class of short peptides 10-20 residues in length that bind to their RNA sites with affinities and specificities approaching those of the intact protein and has been a particularly useful model system for studying principles of RNA-protein interactions (Patel 1999;Frankel 2000;Cheng et al 2001;Das and Frankel 2003). Although referred to as a motif, this class of peptides has no conserved structure and has been shown to bind in a variety of conformations, such as an a-helix in the case of HIV Rev and phage N peptides (Tan et al 1993;Battiste et al 1996;Cai et al 1998;Legault et al 1998), a bhairpin structure in the case of the bovine immunodeficiency virus (BIV) Tat peptide Puglisi et al 1995), and an extended conformation in the case of the HIV Tat peptide (Calnan et al 1991;Aboul-ela et al 1995).…”