File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.15252/embj.2022111857
- Scopus: eid_2-s2.0-85139976395
- WOS: WOS:000892953800011
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation
Title | Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation |
---|---|
Authors | |
Keywords | cryo-electron tomography cryo-EM perforin-2 pore-forming protein subtomogram averaging |
Issue Date | 1-Dec-2022 |
Publisher | EMBO Press |
Citation | The EMBO Journal, 2022, v. 41, n. 23 How to Cite? |
Abstract | Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 β-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion. |
Persistent Identifier | http://hdl.handle.net/10722/338841 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 5.489 |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yu, X | - |
dc.contributor.author | Ni, T | - |
dc.contributor.author | Munson, G | - |
dc.contributor.author | Zhang, P | - |
dc.contributor.author | Gilbert, RJC | - |
dc.date.accessioned | 2024-03-11T10:31:57Z | - |
dc.date.available | 2024-03-11T10:31:57Z | - |
dc.date.issued | 2022-12-01 | - |
dc.identifier.citation | The EMBO Journal, 2022, v. 41, n. 23 | - |
dc.identifier.issn | 0261-4189 | - |
dc.identifier.uri | http://hdl.handle.net/10722/338841 | - |
dc.description.abstract | <p>Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 β-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion.</p> | - |
dc.language | eng | - |
dc.publisher | EMBO Press | - |
dc.relation.ispartof | The EMBO Journal | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | cryo-electron tomography | - |
dc.subject | cryo-EM | - |
dc.subject | perforin-2 | - |
dc.subject | pore-forming protein | - |
dc.subject | subtomogram averaging | - |
dc.title | Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation | - |
dc.type | Article | - |
dc.identifier.doi | 10.15252/embj.2022111857 | - |
dc.identifier.scopus | eid_2-s2.0-85139976395 | - |
dc.identifier.volume | 41 | - |
dc.identifier.issue | 23 | - |
dc.identifier.eissn | 1460-2075 | - |
dc.identifier.isi | WOS:000892953800011 | - |
dc.identifier.issnl | 0261-4189 | - |