LIR motif-containing hyperdisulfide β-ginkgotide is cytoprotective, adaptogenic, and scaffold-ready
Grafting a bioactive peptide onto a disulfide-rich scaffold is a promising approach to improve its structure and metabolic stability. The ginkgo plant-derived β-ginkgotide β-gB1 is a highly unusual molecule: Small, hyperdisulfide, and found only in selected ancient plants. It also contains a conserv...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/10356/79519 http://hdl.handle.net/10220/49718 |
| _version_ | 1826110590887657472 |
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| author | Dutta, Bamaprasad Huang, Jiayi To, Janet Tam, James P. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Dutta, Bamaprasad Huang, Jiayi To, Janet Tam, James P. |
| author_sort | Dutta, Bamaprasad |
| collection | NTU |
| description | Grafting a bioactive peptide onto a disulfide-rich scaffold is a promising approach to improve its structure and metabolic stability. The ginkgo plant-derived β-ginkgotide β-gB1 is a highly unusual molecule: Small, hyperdisulfide, and found only in selected ancient plants. It also contains a conserved 16-amino-acid core with three interlocking disulfides, as well as a six-amino-acid inter-cysteine loop 2 suitable for grafting peptide epitopes. However, very little is known about this recently-discovered family of molecules. Here, we report the biophysical and functional characterizations of the β-ginkgotide β-gB1 from G. biloba. A circular dichroism spectroscopy analysis at 90 °C and proteolytic treatments of β-gB1 supported that it is hyperstable. Data mining revealed that the β-gB1 loop 2 contains the canonical LC3 interacting region (LIR) motif crucial for selective autophagy. Cell-based assays and pull-down experiments showed that β-gB1 is an adaptogen, able to maintain cellular homeostasis through induced autophagosomes formation and to protect cells by targeting intracellular proteins from stress-mediated damage against hypoxia and the hypoxia-reoxygenation of induced cell death. This is the first report of an LIR-containing peptide natural product. Together, our results suggest that the plant-derived β-ginkgotide is cytoprotective, capable of targeting intracellular proteins, and holds promise as a hyperdisulfide scaffold for engineering peptidyl therapeutics with enhanced structural and metabolic stability. |
| first_indexed | 2024-10-01T02:36:59Z |
| format | Journal Article |
| id | ntu-10356/79519 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:36:59Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/795192023-02-28T16:58:44Z LIR motif-containing hyperdisulfide β-ginkgotide is cytoprotective, adaptogenic, and scaffold-ready Dutta, Bamaprasad Huang, Jiayi To, Janet Tam, James P. School of Biological Sciences Science::Biological sciences Adaptogenic Autophagy Grafting a bioactive peptide onto a disulfide-rich scaffold is a promising approach to improve its structure and metabolic stability. The ginkgo plant-derived β-ginkgotide β-gB1 is a highly unusual molecule: Small, hyperdisulfide, and found only in selected ancient plants. It also contains a conserved 16-amino-acid core with three interlocking disulfides, as well as a six-amino-acid inter-cysteine loop 2 suitable for grafting peptide epitopes. However, very little is known about this recently-discovered family of molecules. Here, we report the biophysical and functional characterizations of the β-ginkgotide β-gB1 from G. biloba. A circular dichroism spectroscopy analysis at 90 °C and proteolytic treatments of β-gB1 supported that it is hyperstable. Data mining revealed that the β-gB1 loop 2 contains the canonical LC3 interacting region (LIR) motif crucial for selective autophagy. Cell-based assays and pull-down experiments showed that β-gB1 is an adaptogen, able to maintain cellular homeostasis through induced autophagosomes formation and to protect cells by targeting intracellular proteins from stress-mediated damage against hypoxia and the hypoxia-reoxygenation of induced cell death. This is the first report of an LIR-containing peptide natural product. Together, our results suggest that the plant-derived β-ginkgotide is cytoprotective, capable of targeting intracellular proteins, and holds promise as a hyperdisulfide scaffold for engineering peptidyl therapeutics with enhanced structural and metabolic stability. MOE (Min. of Education, S’pore) Published version 2019-08-21T02:23:09Z 2019-12-06T13:27:18Z 2019-08-21T02:23:09Z 2019-12-06T13:27:18Z 2019 Journal Article Dutta, B., Huang, J., To, J., & Tam, J. P. (2019). LIR Motif-Containing Hyperdisulfide β-Ginkgotide is Cytoprotective, Adaptogenic, and Scaffold-Ready. Molecules, 24(13), 2417-. doi:10.3390/molecules24132417 1420-3049 https://hdl.handle.net/10356/79519 http://hdl.handle.net/10220/49718 10.3390/molecules24132417 en Molecules © 2019 by the Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 14 p. application/pdf |
| spellingShingle | Science::Biological sciences Adaptogenic Autophagy Dutta, Bamaprasad Huang, Jiayi To, Janet Tam, James P. LIR motif-containing hyperdisulfide β-ginkgotide is cytoprotective, adaptogenic, and scaffold-ready |
| title | LIR motif-containing hyperdisulfide β-ginkgotide is cytoprotective, adaptogenic, and scaffold-ready |
| title_full | LIR motif-containing hyperdisulfide β-ginkgotide is cytoprotective, adaptogenic, and scaffold-ready |
| title_fullStr | LIR motif-containing hyperdisulfide β-ginkgotide is cytoprotective, adaptogenic, and scaffold-ready |
| title_full_unstemmed | LIR motif-containing hyperdisulfide β-ginkgotide is cytoprotective, adaptogenic, and scaffold-ready |
| title_short | LIR motif-containing hyperdisulfide β-ginkgotide is cytoprotective, adaptogenic, and scaffold-ready |
| title_sort | lir motif containing hyperdisulfide β ginkgotide is cytoprotective adaptogenic and scaffold ready |
| topic | Science::Biological sciences Adaptogenic Autophagy |
| url | https://hdl.handle.net/10356/79519 http://hdl.handle.net/10220/49718 |
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