Structural basis of dynamic P5CS filaments
The bifunctional enzyme Δ1-pyrroline-5-carboxylate synthase (P5CS) is vital to the synthesis of proline and ornithine, playing an essential role in human health and agriculture. Pathogenic mutations in the P5CS gene (ALDH18A1) lead to neurocutaneous syndrome and skin relaxation connective tissue dis...
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/76107 |
| _version_ | 1811235783162462208 |
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| author | Jiale Zhong Chen-Jun Guo Xian Zhou Chia-Chun Chang Boqi Yin Tianyi Zhang Huan-Huan Hu Guang-Ming Lu Ji-Long Liu |
| author_facet | Jiale Zhong Chen-Jun Guo Xian Zhou Chia-Chun Chang Boqi Yin Tianyi Zhang Huan-Huan Hu Guang-Ming Lu Ji-Long Liu |
| author_sort | Jiale Zhong |
| collection | DOAJ |
| description | The bifunctional enzyme Δ1-pyrroline-5-carboxylate synthase (P5CS) is vital to the synthesis of proline and ornithine, playing an essential role in human health and agriculture. Pathogenic mutations in the P5CS gene (ALDH18A1) lead to neurocutaneous syndrome and skin relaxation connective tissue disease in humans, and P5CS deficiency seriously damages the ability to resist adversity in plants. We have recently found that P5CS forms cytoophidia in vivo and filaments in vitro. However, it is difficult to appreciate the function of P5CS filamentation without precise structures. Using cryo-electron microscopy, here we solve the structures of Drosophila full-length P5CS in three states at resolution from 3.1 to 4.3 Å. We observe distinct ligand-binding states and conformational changes for the GK and GPR domains, respectively. Divergent helical filaments are assembled by P5CS tetramers and stabilized by multiple interfaces. Point mutations disturbing those interfaces prevent P5CS filamentation and greatly reduce the enzymatic activity. Our findings reveal that filamentation is crucial for the coordination between the GK and GPR domains, providing a structural basis for the catalytic function of P5CS filaments. |
| first_indexed | 2024-04-12T11:57:57Z |
| format | Article |
| id | doaj.art-4919bfad814545dfb6cfce7ab23adc0d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T11:57:57Z |
| publishDate | 2022-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4919bfad814545dfb6cfce7ab23adc0d2022-12-22T03:33:56ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.76107Structural basis of dynamic P5CS filamentsJiale Zhong0https://orcid.org/0000-0001-5873-0450Chen-Jun Guo1https://orcid.org/0000-0001-5342-4761Xian Zhou2https://orcid.org/0000-0002-0000-2415Chia-Chun Chang3https://orcid.org/0000-0001-7942-6300Boqi Yin4https://orcid.org/0000-0003-3974-9820Tianyi Zhang5https://orcid.org/0000-0002-4632-6298Huan-Huan Hu6https://orcid.org/0000-0002-5997-530XGuang-Ming Lu7https://orcid.org/0000-0002-6607-2264Ji-Long Liu8https://orcid.org/0000-0002-4834-8554School of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaThe bifunctional enzyme Δ1-pyrroline-5-carboxylate synthase (P5CS) is vital to the synthesis of proline and ornithine, playing an essential role in human health and agriculture. Pathogenic mutations in the P5CS gene (ALDH18A1) lead to neurocutaneous syndrome and skin relaxation connective tissue disease in humans, and P5CS deficiency seriously damages the ability to resist adversity in plants. We have recently found that P5CS forms cytoophidia in vivo and filaments in vitro. However, it is difficult to appreciate the function of P5CS filamentation without precise structures. Using cryo-electron microscopy, here we solve the structures of Drosophila full-length P5CS in three states at resolution from 3.1 to 4.3 Å. We observe distinct ligand-binding states and conformational changes for the GK and GPR domains, respectively. Divergent helical filaments are assembled by P5CS tetramers and stabilized by multiple interfaces. Point mutations disturbing those interfaces prevent P5CS filamentation and greatly reduce the enzymatic activity. Our findings reveal that filamentation is crucial for the coordination between the GK and GPR domains, providing a structural basis for the catalytic function of P5CS filaments.https://elifesciences.org/articles/76107P5CScytoophidiumproline synthesisDrosophilaCryo-EMmetabolic enzyme |
| spellingShingle | Jiale Zhong Chen-Jun Guo Xian Zhou Chia-Chun Chang Boqi Yin Tianyi Zhang Huan-Huan Hu Guang-Ming Lu Ji-Long Liu Structural basis of dynamic P5CS filaments eLife P5CS cytoophidium proline synthesis Drosophila Cryo-EM metabolic enzyme |
| title | Structural basis of dynamic P5CS filaments |
| title_full | Structural basis of dynamic P5CS filaments |
| title_fullStr | Structural basis of dynamic P5CS filaments |
| title_full_unstemmed | Structural basis of dynamic P5CS filaments |
| title_short | Structural basis of dynamic P5CS filaments |
| title_sort | structural basis of dynamic p5cs filaments |
| topic | P5CS cytoophidium proline synthesis Drosophila Cryo-EM metabolic enzyme |
| url | https://elifesciences.org/articles/76107 |
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