Widespread Aggregation and Neurodegenerative Diseases Are Associated with Supersaturated Proteins
The maintenance of protein solubility is a fundamental aspect of cellular homeostasis because protein aggregation is associated with a wide variety of human diseases. Numerous proteins unrelated in sequence and structure, however, can misfold and aggregate, and widespread aggregation can occur in li...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713005664 |
| _version_ | 1828419848610250752 |
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| author | Prajwal Ciryam Gian Gaetano Tartaglia Richard I. Morimoto Christopher M. Dobson Michele Vendruscolo |
| author_facet | Prajwal Ciryam Gian Gaetano Tartaglia Richard I. Morimoto Christopher M. Dobson Michele Vendruscolo |
| author_sort | Prajwal Ciryam |
| collection | DOAJ |
| description | The maintenance of protein solubility is a fundamental aspect of cellular homeostasis because protein aggregation is associated with a wide variety of human diseases. Numerous proteins unrelated in sequence and structure, however, can misfold and aggregate, and widespread aggregation can occur in living systems under stress or aging. A crucial question in this context is why only certain proteins appear to aggregate readily in vivo, whereas others do not. We identify here the proteins most vulnerable to aggregation as those whose cellular concentrations are high relative to their solubilities. We find that these supersaturated proteins represent a metastable subproteome involved in pathological aggregation during stress and aging and are overrepresented in biochemical processes associated with neurodegenerative disorders. Consequently, such cellular processes become dysfunctional when the ability to keep intrinsically supersaturated proteins soluble is compromised. Thus, the simultaneous analysis of abundance and solubility can rationalize the diverse cellular pathologies linked to neurodegenerative diseases and aging. |
| first_indexed | 2024-12-10T15:01:15Z |
| format | Article |
| id | doaj.art-f636dedaca1440e389ed7abd3e2d1aac |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T15:01:15Z |
| publishDate | 2013-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f636dedaca1440e389ed7abd3e2d1aac2022-12-22T01:44:10ZengElsevierCell Reports2211-12472013-11-015378179010.1016/j.celrep.2013.09.043Widespread Aggregation and Neurodegenerative Diseases Are Associated with Supersaturated ProteinsPrajwal Ciryam0Gian Gaetano Tartaglia1Richard I. Morimoto2Christopher M. Dobson3Michele Vendruscolo4Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UKCentre for Genomic Regulation (CRG) and Universitat Pompeu Fabra (UPF), 08003 Barcelona, SpainDepartment of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208-3500, USADepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UKDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UKThe maintenance of protein solubility is a fundamental aspect of cellular homeostasis because protein aggregation is associated with a wide variety of human diseases. Numerous proteins unrelated in sequence and structure, however, can misfold and aggregate, and widespread aggregation can occur in living systems under stress or aging. A crucial question in this context is why only certain proteins appear to aggregate readily in vivo, whereas others do not. We identify here the proteins most vulnerable to aggregation as those whose cellular concentrations are high relative to their solubilities. We find that these supersaturated proteins represent a metastable subproteome involved in pathological aggregation during stress and aging and are overrepresented in biochemical processes associated with neurodegenerative disorders. Consequently, such cellular processes become dysfunctional when the ability to keep intrinsically supersaturated proteins soluble is compromised. Thus, the simultaneous analysis of abundance and solubility can rationalize the diverse cellular pathologies linked to neurodegenerative diseases and aging.http://www.sciencedirect.com/science/article/pii/S2211124713005664 |
| spellingShingle | Prajwal Ciryam Gian Gaetano Tartaglia Richard I. Morimoto Christopher M. Dobson Michele Vendruscolo Widespread Aggregation and Neurodegenerative Diseases Are Associated with Supersaturated Proteins Cell Reports |
| title | Widespread Aggregation and Neurodegenerative Diseases Are Associated with Supersaturated Proteins |
| title_full | Widespread Aggregation and Neurodegenerative Diseases Are Associated with Supersaturated Proteins |
| title_fullStr | Widespread Aggregation and Neurodegenerative Diseases Are Associated with Supersaturated Proteins |
| title_full_unstemmed | Widespread Aggregation and Neurodegenerative Diseases Are Associated with Supersaturated Proteins |
| title_short | Widespread Aggregation and Neurodegenerative Diseases Are Associated with Supersaturated Proteins |
| title_sort | widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713005664 |
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