Crystal structure of a DNA aptamer bound to PvLDH elucidates novel single-stranded DNA structural elements for folding and recognition.

Sung-Jin Choi,Changill Ban

doi:10.1038/srep34998

Abstract

Structural elements are key elements for understanding single-stranded nucleic acid folding. Although various RNA structural elements have been documented, structural elements of single-stranded DNA (ssDNA) have rarely been reported. Herein, we determined a crystal structure of PvLDH in complex with a DNA aptamer called pL1. This aptamer folds into a hairpin-bulge contact by adopting three novel structural elements, viz, DNA T-loop-like motif, base–phosphate zipper, and DNA G·G metal ion zipper. Moreover, the pL1:PvLDH complex shows unique properties compared with other protein:nucleic acid complexes. Generally, extensive intermolecular hydrogen bonds occur between unpaired nucleotides and proteins for specific recognitions. Although most protein-interacting nucleotides of pL1 are unpaired nucleotides, pL1 recognizes PvLDH by predominant shape complementarity with many bridging water molecules owing to the combination of three novel structural elements making protein-binding unpaired nucleotides stable. Moreover, the additional set of Plasmodium LDH residues which were shown to form extensive hydrogen bonds with unpaired nucleotides of 2008s does not participate in the recognition of pL1. Superimposition of the pL1:PvLDH complex with hLDH reveals steric clashes between pL1 and hLDH in contrast with no steric clashes between 2008s and hLDH. Therefore, specific protein recognition mode of pL1 is totally different from that of 2008s.

Highlights

Folded, single-stranded nucleic acid molecules play vital roles in biological processes such as the maintenance of linear DNA length[1], RNA processing, gene expression[2] and ssNA molecules (ssNAs) virus genomes[3]
Unpaired nucleotides in loops and bulges are involved in specific protein recognition through extensive hydrogen bonds (H-bonds) between bases and proteins[25,26,27]
In ssNAs folded into G-quadruplexes and hairpins, hydrogen bonding predominates between unpaired bases and protein surfaces for protein recognition

Summary

Introduction

Single-stranded nucleic acid (ssNA) molecules play vital roles in biological processes such as the maintenance of linear DNA length[1], RNA processing, gene expression[2] and ssNA virus genomes[3]. The crystal structure of PfLDH in a complex with the DNA aptamer 2008s was determined by another group. PL1 folds into a hairpin-bulge contact by adopting three novel structural elements defined as a T-loop-like motif, base–phosphate (BPh) zipper and DNA G·G metal ion zipper.

Results

Conclusion