NMR probing of copper–amyloid β1–16 interactions and self-assembly
Trace metal ions, such as copper, play an important role in the development of amyloid β (Aβ)-mediated Alzheimer’s disease (AD). Atomic-level investigation of Aβ interaction with copper ions is essential for understanding the metal-mediated peptide self-assembly. In this study, we investi...
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2024-12-01
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| author | Punnepalli Sunanda Srinivasarao Raghothama Uma Maheswari Devi Palempalli Bankala Krishnarjuna |
| author_facet | Punnepalli Sunanda Srinivasarao Raghothama Uma Maheswari Devi Palempalli Bankala Krishnarjuna |
| author_sort | Punnepalli Sunanda |
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Trace metal ions, such as copper, play an important role in the development of amyloid β (Aβ)-mediated Alzheimer’s disease (AD). Atomic-level investigation of Aβ interaction with copper ions is essential for understanding the metal-mediated peptide self-assembly. In this study, we investigated copper ion–Aβ1–16 interactions using nuclear magnetic resonance (NMR) spectroscopy, circular dichroism, and transmission electron microscopy. Additionally, we examined the role of copper oxidation states in generating reactive oxygen species (ROS) using a 2′-7′ dichlorofluorescein diacetate (DCFDA) assay. 13C NMR data showed site-specific interactions between copper ions and Aβ1–16, with some differences observed in H2O compared to 2H2O. Aβ1–12, which lacks His13 and His14, was found to interact with copper ions; however, it exhibited increased NMR peak broadening due to nonspecific interactions. While both Cu(II) and Cu(I) delayed Aβ self-assembly, Cu(I) binding to Aβ1–16 or Aβ1–42 resulted in increased ROS production compared to Cu(II). The structural insights provided in this study could contribute to the design and development of new copper ion-specific chelators to reduce excess copper levels and mitigate Aβ-copper-induced neurotoxicity in AD. |
| format | Article |
| id | doaj-art-ec243e465a95490da0b61fb28ac9b522 |
| institution | Kabale University |
| issn | 2837-4010 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Academia.edu Journals |
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| spelling | doaj-art-ec243e465a95490da0b61fb28ac9b5222025-02-11T23:55:59ZengAcademia.edu JournalsAcademia Biology2837-40102024-12-012410.20935/AcadBiol7451NMR probing of copper–amyloid β1–16 interactions and self-assemblyPunnepalli Sunanda0Srinivasarao Raghothama1Uma Maheswari Devi Palempalli2Bankala Krishnarjuna3Department of Applied Microbiology & Biochemistry, Sri Padmavati Mahila Visvavidyalayam, Tirupati, Andhra Pradesh 517502, India.NMR Research Center, Indian Institute of Science, Bangalore, Karnataka 560012, India.Department of Applied Microbiology & Biochemistry, Sri Padmavati Mahila Visvavidyalayam, Tirupati, Andhra Pradesh 517502, India.NMR Research Center, Indian Institute of Science, Bangalore, Karnataka 560012, India. Trace metal ions, such as copper, play an important role in the development of amyloid β (Aβ)-mediated Alzheimer’s disease (AD). Atomic-level investigation of Aβ interaction with copper ions is essential for understanding the metal-mediated peptide self-assembly. In this study, we investigated copper ion–Aβ1–16 interactions using nuclear magnetic resonance (NMR) spectroscopy, circular dichroism, and transmission electron microscopy. Additionally, we examined the role of copper oxidation states in generating reactive oxygen species (ROS) using a 2′-7′ dichlorofluorescein diacetate (DCFDA) assay. 13C NMR data showed site-specific interactions between copper ions and Aβ1–16, with some differences observed in H2O compared to 2H2O. Aβ1–12, which lacks His13 and His14, was found to interact with copper ions; however, it exhibited increased NMR peak broadening due to nonspecific interactions. While both Cu(II) and Cu(I) delayed Aβ self-assembly, Cu(I) binding to Aβ1–16 or Aβ1–42 resulted in increased ROS production compared to Cu(II). The structural insights provided in this study could contribute to the design and development of new copper ion-specific chelators to reduce excess copper levels and mitigate Aβ-copper-induced neurotoxicity in AD.https://www.academia.edu/126438257/NMR_probing_of_copper_amyloid_%CE%B21_16_interactions_and_self_assembly |
| spellingShingle | Punnepalli Sunanda Srinivasarao Raghothama Uma Maheswari Devi Palempalli Bankala Krishnarjuna NMR probing of copper–amyloid β1–16 interactions and self-assembly Academia Biology |
| title | NMR probing of copper–amyloid β1–16 interactions and self-assembly |
| title_full | NMR probing of copper–amyloid β1–16 interactions and self-assembly |
| title_fullStr | NMR probing of copper–amyloid β1–16 interactions and self-assembly |
| title_full_unstemmed | NMR probing of copper–amyloid β1–16 interactions and self-assembly |
| title_short | NMR probing of copper–amyloid β1–16 interactions and self-assembly |
| title_sort | nmr probing of copper amyloid β1 16 interactions and self assembly |
| url | https://www.academia.edu/126438257/NMR_probing_of_copper_amyloid_%CE%B21_16_interactions_and_self_assembly |
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