High-resolution structural-omics of human liver enzymes
Summary: We applied raw human liver microsome lysate to a holey carbon grid and used cryo-electron microscopy (cryo-EM) to define its composition. From this sample we identified and simultaneously determined high-resolution structural information for ten unique human liver enzymes involved in divers...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723006204 |
| _version_ | 1827930488112676864 |
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| author | Chih-Chia Su Meinan Lyu Zhemin Zhang Masaru Miyagi Wei Huang Derek J. Taylor Edward W. Yu |
| author_facet | Chih-Chia Su Meinan Lyu Zhemin Zhang Masaru Miyagi Wei Huang Derek J. Taylor Edward W. Yu |
| author_sort | Chih-Chia Su |
| collection | DOAJ |
| description | Summary: We applied raw human liver microsome lysate to a holey carbon grid and used cryo-electron microscopy (cryo-EM) to define its composition. From this sample we identified and simultaneously determined high-resolution structural information for ten unique human liver enzymes involved in diverse cellular processes. Notably, we determined the structure of the endoplasmic bifunctional protein H6PD, where the N- and C-terminal domains independently possess glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase enzymatic activity, respectively. We also obtained the structure of heterodimeric human GANAB, an ER glycoprotein quality-control machinery that contains a catalytic α subunit and a noncatalytic β subunit. In addition, we observed a decameric peroxidase, PRDX4, which directly contacts a disulfide isomerase-related protein, ERp46. Structural data suggest that several glycosylations, bound endogenous compounds, and ions associate with these human liver enzymes. These results highlight the importance of cryo-EM in facilitating the elucidation of human organ proteomics at the atomic level. |
| first_indexed | 2024-03-13T06:37:24Z |
| format | Article |
| id | doaj.art-c332cee5b6a040d4929941c9dbb12793 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T06:37:24Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c332cee5b6a040d4929941c9dbb127932023-06-09T04:27:47ZengElsevierCell Reports2211-12472023-06-01426112609High-resolution structural-omics of human liver enzymesChih-Chia Su0Meinan Lyu1Zhemin Zhang2Masaru Miyagi3Wei Huang4Derek J. Taylor5Edward W. Yu6Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USADepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USADepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USADepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USADepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USADepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USADepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Corresponding authorSummary: We applied raw human liver microsome lysate to a holey carbon grid and used cryo-electron microscopy (cryo-EM) to define its composition. From this sample we identified and simultaneously determined high-resolution structural information for ten unique human liver enzymes involved in diverse cellular processes. Notably, we determined the structure of the endoplasmic bifunctional protein H6PD, where the N- and C-terminal domains independently possess glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase enzymatic activity, respectively. We also obtained the structure of heterodimeric human GANAB, an ER glycoprotein quality-control machinery that contains a catalytic α subunit and a noncatalytic β subunit. In addition, we observed a decameric peroxidase, PRDX4, which directly contacts a disulfide isomerase-related protein, ERp46. Structural data suggest that several glycosylations, bound endogenous compounds, and ions associate with these human liver enzymes. These results highlight the importance of cryo-EM in facilitating the elucidation of human organ proteomics at the atomic level.http://www.sciencedirect.com/science/article/pii/S2211124723006204CP: Molecular biologyCP: Metabolism |
| spellingShingle | Chih-Chia Su Meinan Lyu Zhemin Zhang Masaru Miyagi Wei Huang Derek J. Taylor Edward W. Yu High-resolution structural-omics of human liver enzymes Cell Reports CP: Molecular biology CP: Metabolism |
| title | High-resolution structural-omics of human liver enzymes |
| title_full | High-resolution structural-omics of human liver enzymes |
| title_fullStr | High-resolution structural-omics of human liver enzymes |
| title_full_unstemmed | High-resolution structural-omics of human liver enzymes |
| title_short | High-resolution structural-omics of human liver enzymes |
| title_sort | high resolution structural omics of human liver enzymes |
| topic | CP: Molecular biology CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723006204 |
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