Cryo-electron microscopy structure of a human PRMT5:MEP50 complex.
Protein arginine methyl transferase 5 (PRMT5) is a signaling protein and histone modifying enzyme that is important in many cellular processes, including regulation of eukaryotic gene transcription. Reported here is a 3.7 Å structure of PRMT5, solved in complex with regulatory binding subunit MEP50...
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| Format: | Article |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5843215?pdf=render |
| _version_ | 1818319817401171968 |
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| author | David E Timm Valorie Bowman Russell Madsen Charles Rauch |
| author_facet | David E Timm Valorie Bowman Russell Madsen Charles Rauch |
| author_sort | David E Timm |
| collection | DOAJ |
| description | Protein arginine methyl transferase 5 (PRMT5) is a signaling protein and histone modifying enzyme that is important in many cellular processes, including regulation of eukaryotic gene transcription. Reported here is a 3.7 Å structure of PRMT5, solved in complex with regulatory binding subunit MEP50 (methylosome associated protein 50, WDR77, p44), by single particle (SP) cryo-Electron Microscopy (cryo-EM) using micrographs of particles that are visibly crowded and aggregated. Despite suboptimal micrograph appearance, this cryo-EM structure is in good agreement with previously reported crystal structures of the complex, which revealed a 450 kDa hetero-octameric assembly having internal D2 symmetry. The catalytic PRMT5 subunits form a core tetramer and the MEP50 subunits are arranged peripherally in complex with the PRMT5 N-terminal domain. The cryo-EM reconstruction shows good side chain definition and shows a well-resolved peak for a bound dehydrosinefungin inhibitor molecule. These results demonstrate the applicability of cryo-EM in determining structures of human protein complexes of biomedical significance and suggests cryo-EM could be further utilized to understand PRMT5 interactions with other biologically important binding proteins and ligands. |
| first_indexed | 2024-12-13T10:15:08Z |
| format | Article |
| id | doaj.art-35bf377557b644c2a9f021413c24eb4b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T10:15:08Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-35bf377557b644c2a9f021413c24eb4b2022-12-21T23:51:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01133e019320510.1371/journal.pone.0193205Cryo-electron microscopy structure of a human PRMT5:MEP50 complex.David E TimmValorie BowmanRussell MadsenCharles RauchProtein arginine methyl transferase 5 (PRMT5) is a signaling protein and histone modifying enzyme that is important in many cellular processes, including regulation of eukaryotic gene transcription. Reported here is a 3.7 Å structure of PRMT5, solved in complex with regulatory binding subunit MEP50 (methylosome associated protein 50, WDR77, p44), by single particle (SP) cryo-Electron Microscopy (cryo-EM) using micrographs of particles that are visibly crowded and aggregated. Despite suboptimal micrograph appearance, this cryo-EM structure is in good agreement with previously reported crystal structures of the complex, which revealed a 450 kDa hetero-octameric assembly having internal D2 symmetry. The catalytic PRMT5 subunits form a core tetramer and the MEP50 subunits are arranged peripherally in complex with the PRMT5 N-terminal domain. The cryo-EM reconstruction shows good side chain definition and shows a well-resolved peak for a bound dehydrosinefungin inhibitor molecule. These results demonstrate the applicability of cryo-EM in determining structures of human protein complexes of biomedical significance and suggests cryo-EM could be further utilized to understand PRMT5 interactions with other biologically important binding proteins and ligands.http://europepmc.org/articles/PMC5843215?pdf=render |
| spellingShingle | David E Timm Valorie Bowman Russell Madsen Charles Rauch Cryo-electron microscopy structure of a human PRMT5:MEP50 complex. PLoS ONE |
| title | Cryo-electron microscopy structure of a human PRMT5:MEP50 complex. |
| title_full | Cryo-electron microscopy structure of a human PRMT5:MEP50 complex. |
| title_fullStr | Cryo-electron microscopy structure of a human PRMT5:MEP50 complex. |
| title_full_unstemmed | Cryo-electron microscopy structure of a human PRMT5:MEP50 complex. |
| title_short | Cryo-electron microscopy structure of a human PRMT5:MEP50 complex. |
| title_sort | cryo electron microscopy structure of a human prmt5 mep50 complex |
| url | http://europepmc.org/articles/PMC5843215?pdf=render |
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