Studies on Copper and Aβ1-16-Induced Conformational Changes in CAG/CTG Trinucleotide Repeats Sequence

M Govindaraju; K S Rao Jayanth; D Jagadeesh Kumar; U J S Prasada Rao; K R S Sambasiva Rao; K S Rao

doi:10.3233/ADR-170027

Studies on Copper and Aβ_1-16-Induced Conformational Changes in CAG/CTG Trinucleotide Repeats Sequence

J Alzheimers Dis Rep. 2017 Dec 29;1(1):277-286. doi: 10.3233/ADR-170027.

Authors

M Govindaraju¹, K S Rao Jayanth^{2

3}, D Jagadeesh Kumar⁴, U J S Prasada Rao⁵, K R S Sambasiva Rao⁶, K S Rao²

Affiliations

¹ Department of Molecular Biophysics, Indian Institute of Science, Bangalore, India.
² Center for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), City of Knowledge, Republic of Panama.
³ Undergraduate Student, University of Missouri Kansas City (UMKC), Kansas City, MO, USA.
⁴ Department of Biotechnology, Sir M. Visvesvaraya Institute of Technology, Bangalore, India.
⁵ Department of Biochemistry, CSIR-Central Food Technological Research Institute (CFTRI), Mysore, India.
⁶ Department of Biotechnology, Acharya Nagarjuna University, Guntur, India.

Abstract

DNA conformation and stability are critical for the normal cell functions, which control many cellular processes in life, such as replication, transcription, DNA repair, etc. The accumulation of amyloid-β peptide (Aβ) and Copper (Cu) are the etiological factors for neurodegenerative diseases and hypothesized that they can cause DNA instability. In the current investigation, we studied copper and Aβ_1-16 induced conformation and stability changes in CAG/CTG sequences and found alterations from B-DNA to altered B-conformation. Further, the interaction of the copper and Aβ_1-16 with CAG/CTG sequences was studied by molecular docking modeling and results indicated that the interaction of copper and Aβ_1-16 was through the hydrogen bond formation between adenine, guanine, and cytocine. This study illustrates the role of the copper and Aβ_1-16 in modulating the DNA conformation and stability.

Keywords: Circular dichroism; conformation; neurodegeneration; trinucleotides.