دورية أكاديمية
Characterizing the amyloid core region of the tumor suppressor protein p16 INK4a using a limited proteolysis and peptide-based approach.
| العنوان: | Characterizing the amyloid core region of the tumor suppressor protein p16 INK4a using a limited proteolysis and peptide-based approach. |
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| المؤلفون: | Heath SG; Mātai Hāora - Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand., Naughton JD; Mātai Hāora - Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand., Magon NJ; Mātai Hāora - Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand., Gray SG; School of Biological Sciences, University of Canterbury, Christchurch, New Zealand., Smith BR; Mātai Hāora - Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand., Morris VK; School of Biological Sciences, University of Canterbury, Christchurch, New Zealand; Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand. Electronic address: vanessa.morris@canterbury.ac.nz., Göbl C; Mātai Hāora - Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand; Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand. Electronic address: christoph.goebl@otago.ac.nz. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2024 Jul 18; Vol. 300 (8), pp. 107590. Date of Electronic Publication: 2024 Jul 18. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مستخلص: | The human tumor suppressor p16 INK4a is a small monomeric protein that can form amyloid structures. Formation of p16 INK4a amyloid fibrils is induced by oxidation which creates an intermolecular disulfide bond. The conversion into amyloid is associated with a change from an all α-helical structure into β-sheet fibrils. Currently, structural insights into p16 INK4a amyloid fibrils are lacking. Here, we investigate the amyloid-forming regions of this tumor suppressor using isotope-labeling limited-digestion mass spectrometry analysis. We discover two key regions that likely form the structured core of the amyloid. Further investigations using thioflavin-T fluorescence assays, electron microscopy, and solution nuclear magnetic resonance spectroscopy of shorter peptide regions confirm the self-assembly of the identified sequences that include methionine and leucine repeat regions. This work describes a simple approach for studying protein motifs involved in the conversion of monomeric species into aggregated fibril structures. It provides insight into the polypeptide sequence underlying the core structure of amyloid p16 INK4a formed after a unique oxidation-driven structural transition. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: amyloid; mass spectrometry; p16(INK4a); protein oxidation; protein stability |
| تواريخ الأحداث: | Date Created: 20240720 Latest Revision: 20240815 |
| رمز التحديث: | 20240816 |
| DOI: | 10.1016/j.jbc.2024.107590 |
| PMID: | 39032649 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2024.107590 |