Title: insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptides
Abstract Background Protein aggregation is a biological event observed in expression systems in which the recombinant protein is produced under stressful conditions surpassing the homeostasis of the protein quality control system. In addition, protein aggregation is also related to conformational di...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12934-021-01524-3 |
| _version_ | 1818326772615217152 |
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| author | Jose Vicente Carratalá Andrés Cisneros Elijah Hellman Antonio Villaverde Neus Ferrer-Miralles |
| author_facet | Jose Vicente Carratalá Andrés Cisneros Elijah Hellman Antonio Villaverde Neus Ferrer-Miralles |
| author_sort | Jose Vicente Carratalá |
| collection | DOAJ |
| description | Abstract Background Protein aggregation is a biological event observed in expression systems in which the recombinant protein is produced under stressful conditions surpassing the homeostasis of the protein quality control system. In addition, protein aggregation is also related to conformational diseases in animals as transmissible prion diseases or non-transmissible neurodegenerative diseases including Alzheimer, Parkinson’s disease, amyloidosis and multiple system atrophy among others. At the molecular level, the presence of aggregation-prone domains in protein molecules act as seeding igniters to induce the accumulation of protein molecules in protease-resistant clusters by intermolecular interactions. Results In this work we have studied the aggregating-prone performance of a small peptide (L6K2) with additional antimicrobial activity and we have elucidated the relevance of the accompanying scaffold protein to enhance the aggregating profile of the fusion protein. Furthermore, we demonstrated that the fusion of L6K2 to highly soluble recombinant proteins directs the protein to inclusion bodies (IBs) in E. coli through stereospecific interactions in the presence of an insoluble protein displaying the same aggregating-prone peptide (APP). Conclusions These data suggest that the molecular bases of protein aggregation are related to the net balance of protein aggregation potential and not only to the presence of APPs. This is then presented as a generic platform to generate hybrid protein aggregates in microbial cell factories for biopharmaceutical and biotechnological applications. |
| first_indexed | 2024-12-13T12:05:41Z |
| format | Article |
| id | doaj.art-2e30329942f44de89cd5ede91c147546 |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-12-13T12:05:41Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-2e30329942f44de89cd5ede91c1475462022-12-21T23:46:58ZengBMCMicrobial Cell Factories1475-28592021-02-0120111010.1186/s12934-021-01524-3Title: insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptidesJose Vicente Carratalá0Andrés Cisneros1Elijah Hellman2Antonio Villaverde3Neus Ferrer-Miralles4Institute for Biotechnology and Biomedicine, Autonomous University of BarcelonaInstitute for Biotechnology and Biomedicine, Autonomous University of BarcelonaInstitute for Biotechnology and Biomedicine, Autonomous University of BarcelonaInstitute for Biotechnology and Biomedicine, Autonomous University of BarcelonaInstitute for Biotechnology and Biomedicine, Autonomous University of BarcelonaAbstract Background Protein aggregation is a biological event observed in expression systems in which the recombinant protein is produced under stressful conditions surpassing the homeostasis of the protein quality control system. In addition, protein aggregation is also related to conformational diseases in animals as transmissible prion diseases or non-transmissible neurodegenerative diseases including Alzheimer, Parkinson’s disease, amyloidosis and multiple system atrophy among others. At the molecular level, the presence of aggregation-prone domains in protein molecules act as seeding igniters to induce the accumulation of protein molecules in protease-resistant clusters by intermolecular interactions. Results In this work we have studied the aggregating-prone performance of a small peptide (L6K2) with additional antimicrobial activity and we have elucidated the relevance of the accompanying scaffold protein to enhance the aggregating profile of the fusion protein. Furthermore, we demonstrated that the fusion of L6K2 to highly soluble recombinant proteins directs the protein to inclusion bodies (IBs) in E. coli through stereospecific interactions in the presence of an insoluble protein displaying the same aggregating-prone peptide (APP). Conclusions These data suggest that the molecular bases of protein aggregation are related to the net balance of protein aggregation potential and not only to the presence of APPs. This is then presented as a generic platform to generate hybrid protein aggregates in microbial cell factories for biopharmaceutical and biotechnological applications.https://doi.org/10.1186/s12934-021-01524-3Recombinant proteinInclusion body formationProtein aggregationIntermolecular interactionAntimicrobial peptides |
| spellingShingle | Jose Vicente Carratalá Andrés Cisneros Elijah Hellman Antonio Villaverde Neus Ferrer-Miralles Title: insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptides Microbial Cell Factories Recombinant protein Inclusion body formation Protein aggregation Intermolecular interaction Antimicrobial peptides |
| title | Title: insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptides |
| title_full | Title: insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptides |
| title_fullStr | Title: insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptides |
| title_full_unstemmed | Title: insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptides |
| title_short | Title: insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptides |
| title_sort | title insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptides |
| topic | Recombinant protein Inclusion body formation Protein aggregation Intermolecular interaction Antimicrobial peptides |
| url | https://doi.org/10.1186/s12934-021-01524-3 |
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