Interaction of Prion Peptides with DNA Structures

Anshula Tandon; Vinod Kumar Subramani; Kyeong Kyu Kim; Sung Ha Park

doi:10.1021/acsomega.1c04328

Interaction of Prion Peptides with DNA Structures

ACS Omega. 2021 Dec 20;7(1):176-186. doi: 10.1021/acsomega.1c04328. eCollection 2022 Jan 11.

Authors

Anshula Tandon^{1

2}, Vinod Kumar Subramani³, Kyeong Kyu Kim^{2

3}, Sung Ha Park^{1

2}

Affiliations

¹ Department of Physics, Sungkyunkwan University, Suwon 16419, Korea.
² Sungkyunkwan Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon 16419, Korea.
³ Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Korea.

Abstract

Prion protein aggregation is known to be modulated by macromolecules including nucleic acids. To clarify the role of nucleic acids in PrP pathology, we investigated the interaction between nucleic acids and the prion peptide (PrP)-a synthetic prion protein model peptide resembling a portion of the human prion protein in structure and function spanning amino acid residues 106-126. We used synthetic DNA lattices and natural DNA duplexes extracted from salmon (sDNA) bound with PrP and studied their interaction using distinct physical measurements. The formation of DNA lattices with PrP was visualized by atomic force microscopy (AFM) to investigate the influence of the PrP. PrP inhibited the growth of the double-crossover (DX) lattices significantly compared to the control peptide (CoP). We also conducted optical measurements such as ultraviolet-visible (UV-Vis), circular dichroism (CD), and Fourier transform infrared (FTIR) spectroscopies to validate the interaction between PrP and DNA immediately (D₀) and after a 30-day incubation (D₃₀) period. UV-Vis spectra showed variation in the absorbance intensities, specific for the binding of CoP and PrP to DNA. The CD analysis revealed the presence of various secondary structures, such as α-helices and β-sheets, in PrP- and PrP-bound sDNA complexes. The PrP-sDNA interaction was confirmed using FTIR by the change and shift of the absorption peak intensity and the alteration of PrP secondary structures in the presence of DNA. The cytotoxic effects of the PrP-bound sDNA complexes were assessed by a cytotoxicity assay in human neuroblastoma cells in culture. It confirmed that PrP with sDNA was less cytotoxic than CoP. This study provides new applications for DNA molecules by investigating their effect in complex with aggregated proteins. Our study unequivocally showed the beneficial effect of the interaction between DNA and the pathological prion protein. It therefore provides valuable information to exploit this effect in the development of potential therapeutics. Moreover, our work might serve as a basis for further studies investigating the role of DNA interactions with other amyloidogenic proteins.