Recent advances in understanding mammalian prion structure: a mini review
Prions are lethal pathogens, which cause fatal neurodegenerative diseases in mammals. They are unique infectious agents and are composed of self-propagating multi-chain assemblies of misfolded host-encoded prion protein (PrP). Understanding prion structure is fundamental to understanding prion disea...
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| Format: | Article |
| Language: | English |
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Frontiers Media
2019
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| Online Access: | https://repository.londonmet.ac.uk/5046/1/fnmol-12-00169.pdf |
| _version_ | 1825625390411939840 |
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| author | Terry, Cassandra Wadsworth, Jonathan D. F. |
| author_facet | Terry, Cassandra Wadsworth, Jonathan D. F. |
| author_sort | Terry, Cassandra |
| collection | LMU |
| description | Prions are lethal pathogens, which cause fatal neurodegenerative diseases in mammals. They are unique infectious agents and are composed of self-propagating multi-chain assemblies of misfolded host-encoded prion protein (PrP). Understanding prion structure is fundamental to understanding prion disease pathogenesis however to date, the high-resolution structure of authentic infectious prions remains unknown. Advances in determining prion structure have been severely impeded by the difficulty in recovering relatively homogeneous prion particles from infected brain and definitively associating infectivity with the PrP assembly state. Recently, however, images of highly infectious PrP rods that produce prion-strain specific disease phenotypes in mice have been obtained using cryo-electron microscopy and atomic force microscopy. These images have provided the most detailed description of mammalian prions reported to date and have established that prions isolated from multiple strains have a common hierarchical structure. Misfolded PrP is assembled into 20 nm wide rods containing two fibers, each with double helical repeating substructure, separated by a characteristic central gap 8-10 nm in width. Irregularly structured material with adhesive properties distinct to that of the fibers is present within the central gap of the rod. Prions are clearly distinguishable from non-infectious recombinant PrP fibrils generated and from all other propagating protein structures so far described in other neurodegenerative diseases. The basic architecture of mammalian prions appears to be exceptional and fundamental to their lethal pathogenicity. |
| first_indexed | 2024-07-09T03:58:40Z |
| format | Article |
| id | oai:repository.londonmet.ac.uk:5046 |
| institution | London Metropolitan University |
| language | English |
| last_indexed | 2024-07-09T03:58:40Z |
| publishDate | 2019 |
| publisher | Frontiers Media |
| record_format | eprints |
| spelling | oai:repository.londonmet.ac.uk:50462019-09-18T11:53:07Z https://repository.londonmet.ac.uk/5046/ Recent advances in understanding mammalian prion structure: a mini review Terry, Cassandra Wadsworth, Jonathan D. F. 570 Life sciences; biology 610 Medicine & health Prions are lethal pathogens, which cause fatal neurodegenerative diseases in mammals. They are unique infectious agents and are composed of self-propagating multi-chain assemblies of misfolded host-encoded prion protein (PrP). Understanding prion structure is fundamental to understanding prion disease pathogenesis however to date, the high-resolution structure of authentic infectious prions remains unknown. Advances in determining prion structure have been severely impeded by the difficulty in recovering relatively homogeneous prion particles from infected brain and definitively associating infectivity with the PrP assembly state. Recently, however, images of highly infectious PrP rods that produce prion-strain specific disease phenotypes in mice have been obtained using cryo-electron microscopy and atomic force microscopy. These images have provided the most detailed description of mammalian prions reported to date and have established that prions isolated from multiple strains have a common hierarchical structure. Misfolded PrP is assembled into 20 nm wide rods containing two fibers, each with double helical repeating substructure, separated by a characteristic central gap 8-10 nm in width. Irregularly structured material with adhesive properties distinct to that of the fibers is present within the central gap of the rod. Prions are clearly distinguishable from non-infectious recombinant PrP fibrils generated and from all other propagating protein structures so far described in other neurodegenerative diseases. The basic architecture of mammalian prions appears to be exceptional and fundamental to their lethal pathogenicity. Frontiers Media 2019-07-09 Article PeerReviewed text en https://repository.londonmet.ac.uk/5046/1/fnmol-12-00169.pdf Terry, Cassandra and Wadsworth, Jonathan D. F. (2019) Recent advances in understanding mammalian prion structure: a mini review. Frontiers in molecular neuroscience, 12. pp. 169-176. ISSN 1662-5099 10.3389/fnmol.2019.00169 10.3389/fnmol.2019.00169 |
| spellingShingle | 570 Life sciences; biology 610 Medicine & health Terry, Cassandra Wadsworth, Jonathan D. F. Recent advances in understanding mammalian prion structure: a mini review |
| title | Recent advances in understanding mammalian prion structure: a mini review |
| title_full | Recent advances in understanding mammalian prion structure: a mini review |
| title_fullStr | Recent advances in understanding mammalian prion structure: a mini review |
| title_full_unstemmed | Recent advances in understanding mammalian prion structure: a mini review |
| title_short | Recent advances in understanding mammalian prion structure: a mini review |
| title_sort | recent advances in understanding mammalian prion structure a mini review |
| topic | 570 Life sciences; biology 610 Medicine & health |
| url | https://repository.londonmet.ac.uk/5046/1/fnmol-12-00169.pdf |
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