Home
This Title All WIREs
WIREs RSS Feed
How to cite this WIREs title:
WIREs RNA
Impact Factor: 4.928

Expected and unexpected features of protein‐binding RNA aptamers

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

RNA molecules with high affinity to specific proteins can be isolated from libraries of up to 1016 different RNA sequences by systematic evolution of ligands by exponential enrichment (SELEX). These so‐called protein‐binding RNA aptamers are often interesting, e.g., as modulators of protein function for therapeutic use, for probing the conformations of proteins, for studies of basic aspects of nucleic acid–protein interactions, etc. Studies on the interactions between RNA aptamers and proteins display a number of expected and unexpected features, including the chemical nature of the interacting RNA‐protein surfaces, the conformation of protein‐bound aptamer versus free aptamer, the conformation of aptamer‐bound protein versus free protein, and the effects of aptamers on protein function. Here, we review current insights into the details of RNA aptamer–protein interactions. WIREs RNA 2016, 7:744–757. doi: 10.1002/wrna.1360 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
Surface electrostatic potentials of aptamer‐binding proteins. Electrostatic potential maps are shown for the protein targets of (a) Toggle‐25t (PDB ID 3DD2), (b) anti‐hFc1 (PDB ID 3AGV), and (c) Lys1 (PDB ID 4M4O) aptamers. Red indicates negative, while blue indicates positive surface patches. Aptamers are shown as orange phosphate backbone traces, with bases as blue‐green ladders. The figure was constructed using PyMol Viewer.
[ Normal View | Magnified View ]
An aptamer to PAI‐1 induces structural stability in regions outside the binding site. PAI‐1 (PDB ID 3Q02) is shown in a cartoon representation with the regions most stabilized by the aptamer paionap‐40 highlighted according to hydrogen/deuterium exchange analysis (green and blue: 20–29% and >30% lower exchange rate with paionap‐40 relative to control RNA, respectively). For the complete hydrogen/exchange profile, see the original article. The binding site residues of paionap‐40, which were identified by alanine scanning mutagenesis, are shown as red spheres (Arg76, Lys80, Phe114, Arg118, Lys122).
[ Normal View | Magnified View ]
Adaptive binding of RNA‐2 to ribosomal protein S8. The phosphate backbone of RNA‐2 adopts a distinct conformation upon binding to its target. An overview of the aptamer‐protein complex (PDB ID 4PDB) is shown in (a), with r‐protein S8 as a white silhouette, and the bound aptamer (red) aligned with the ligand‐free RNA‐2 structure (blue; PDB ID 2LUN). Several internal arrangements are shifted in the complexed structure in order to stabilize the altered conformation. For instance, a G‐(G‐C) base triple is not formed in the absence of r‐protein S8 (b). Base triple nucleotides are shown in sticks. The figure was constructed using PyMol Viewer.
[ Normal View | Magnified View ]
Adaptive binding of an NF‐κB‐binding aptamer. The X‐ray crystal structure of the aptamer (PDB ID 1OOA; red backbone trace, with the apical loop shown as red sticks) in complex with NF‐κB (not shown) was aligned to the NMR solution structure (PDB ID 2JWV; blue) of the free aptamer, based on the protein‐binding regions neighboring the terminal GUAA tetraloop. Upon aptamer‐protein complex formation, structural changes in the internal loop induce a kink in the helical portion of the aptamer fold (a) and the apical tetraloop undergoes a conformational change (b). The figure was constructed using PyMol Viewer.
[ Normal View | Magnified View ]
An aptamer mimics the natural interaction between ATP and a kinase by adenine insertion and phosphate isostery. (a) Adenine 51 (sticks) of the aptamer C13.18 enters the ATP‐binding pocket of GRK2 (PDB ID 3UZT). The phosphate (sticks) connecting A49 (not shown) and U50 (sticks) contacts Asp335 (white sticks in the background) via a bridging Mg2+ion (blue sphere). (b) The position of monomeric ATP in complex with GRK2 (PDB ID 3C4W) is identical to A51 in the C13.18 complex. The γ‐phosphate of ATP is isosteric with the A49‐U50 backbone phosphate of C13.18, and contacts Asp335 in an identical way. The coloring of the GRK2 surface in both depictions indicates the electrostatic potential, red being negative, blue positive. The figure was constructed using PyMol Viewer.
[ Normal View | Magnified View ]
Double‐stranded DNA mimicry by an NF‐κB binding RNA aptamer. A monomeric p50 subunit of NF‐κB is shown in complex with dsDNA (PDB ID 2V2T) (a) and an RNA aptamer (PDB ID 1OOA) (b). The figure was constructed using PyMol Viewer.
[ Normal View | Magnified View ]
Apt1‐S2 mimics the runt‐binding dsDNA element of AML1. Two C‐G base pairs and an unpaired G in the solution structure of Apt1‐S2 (blue; PDB ID 2RRC) are isosteric with an identical arrangement in the structure of a dsDNA fragment containing the consensus RDE sequence in complex with the Runt domain of AML1 (red; PDB ID 1HJC). Aptamer base positions are indicated. The figure was constructed using PyMol Viewer.
[ Normal View | Magnified View ]
A ribosomal protein S8‐binding aptamer mimics the interface of the natural RNA ligand‐S8 interface. RNA‐2, an aptamer selected for binding to ribosomal protein S8, resembles spc mRNA when associated with its target, despite limited sequence homology. (a) The phosphate backbone trace of spc mRNA (blue) is closely mirrored by RNA‐2 (red) in the protein‐binding region. Ribosomal protein S8 is shown in cartoon representation. The aptamer fold is stabilized by a base triplet (b) and quartet (c), both of which display many similarities with the intramolecular structures of spc mRNA. The identity and position of participating nucleotides in the aptamer are indicated, with the identity of the equivalent position in spc mRNA given in parenthesis. The figure was constructed using PyMol Viewer and PDB ID 1S03 (spc mRNA complex) and 2LUN (aptamer complex).
[ Normal View | Magnified View ]
Toggle‐25t binding to thrombin is mediated by an extended intercalating structure. A continuous π‐π stack, almost 30 Å in length, composed of adenines and guanines (blue sticks) from the aptamer, and two arginine residues (green sticks) of thrombin (white silhouette) is a central feature of the aptamer‐protein complex. The figure was constructed using PyMol Viewer and the PDB ID 3DD2.
[ Normal View | Magnified View ]

Browse by Topic

RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes
RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts