Structural basis for membrane microdomain formation by a human Stomatin complex
Abstract Biological membranes are not just passive barriers—they actively sense and respond to mechanical forces, in part through specialized proteins embedded within them. Among these are Stomatin-family proteins, which are known to influence membrane stiffness and regulate ion channels, yet how th...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62859-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849332543490359296 |
|---|---|
| author | Jack Stoner Shufang Li Ziao Fu |
| author_facet | Jack Stoner Shufang Li Ziao Fu |
| author_sort | Jack Stoner |
| collection | DOAJ |
| description | Abstract Biological membranes are not just passive barriers—they actively sense and respond to mechanical forces, in part through specialized proteins embedded within them. Among these are Stomatin-family proteins, which are known to influence membrane stiffness and regulate ion channels, yet how they achieve these functions at the molecular level has remained elusive. Here, we report the 2.2 Å cryo-electron microscopy structure of the human Stomatin complex in a native membrane environment. We find that Stomatin assembles into a 16-subunit ring-shaped homo-oligomer, forming a ~12 nm-wide cage that defines a mechanically distinct, curvature-resistant membrane microdomain. While the majority of the complex exhibits C16 symmetry, the C-terminal domains adopt two alternating conformations, producing a symmetry-broken hydrophobic β-barrel pore with local C8 symmetry. The membrane beneath the complex remains flat despite surrounding curvature, indicating localized membrane stiffening. The structure reveals a conserved network of inter-subunit salt bridges that stabilize the assembly. These findings provide a molecular framework for how Stomatin oligomers shape membrane architecture and mechanics, offering insight into their roles in mechanotransduction and diseases such as nephrotic syndrome. |
| format | Article |
| id | doaj-art-8a5f284c445a45bc9fae000510a6c0a6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8a5f284c445a45bc9fae000510a6c0a62025-08-20T03:46:09ZengNature PortfolioNature Communications2041-17232025-08-011611910.1038/s41467-025-62859-8Structural basis for membrane microdomain formation by a human Stomatin complexJack Stoner0Shufang Li1Ziao Fu2Center for the Investigation of Membrane Excitability Diseases, Washington University School of MedicineDepartment of Pediatrics, St Louis Children’s Hospital, Washington University School of MedicineCenter for the Investigation of Membrane Excitability Diseases, Washington University School of MedicineAbstract Biological membranes are not just passive barriers—they actively sense and respond to mechanical forces, in part through specialized proteins embedded within them. Among these are Stomatin-family proteins, which are known to influence membrane stiffness and regulate ion channels, yet how they achieve these functions at the molecular level has remained elusive. Here, we report the 2.2 Å cryo-electron microscopy structure of the human Stomatin complex in a native membrane environment. We find that Stomatin assembles into a 16-subunit ring-shaped homo-oligomer, forming a ~12 nm-wide cage that defines a mechanically distinct, curvature-resistant membrane microdomain. While the majority of the complex exhibits C16 symmetry, the C-terminal domains adopt two alternating conformations, producing a symmetry-broken hydrophobic β-barrel pore with local C8 symmetry. The membrane beneath the complex remains flat despite surrounding curvature, indicating localized membrane stiffening. The structure reveals a conserved network of inter-subunit salt bridges that stabilize the assembly. These findings provide a molecular framework for how Stomatin oligomers shape membrane architecture and mechanics, offering insight into their roles in mechanotransduction and diseases such as nephrotic syndrome.https://doi.org/10.1038/s41467-025-62859-8 |
| spellingShingle | Jack Stoner Shufang Li Ziao Fu Structural basis for membrane microdomain formation by a human Stomatin complex Nature Communications |
| title | Structural basis for membrane microdomain formation by a human Stomatin complex |
| title_full | Structural basis for membrane microdomain formation by a human Stomatin complex |
| title_fullStr | Structural basis for membrane microdomain formation by a human Stomatin complex |
| title_full_unstemmed | Structural basis for membrane microdomain formation by a human Stomatin complex |
| title_short | Structural basis for membrane microdomain formation by a human Stomatin complex |
| title_sort | structural basis for membrane microdomain formation by a human stomatin complex |
| url | https://doi.org/10.1038/s41467-025-62859-8 |
| work_keys_str_mv | AT jackstoner structuralbasisformembranemicrodomainformationbyahumanstomatincomplex AT shufangli structuralbasisformembranemicrodomainformationbyahumanstomatincomplex AT ziaofu structuralbasisformembranemicrodomainformationbyahumanstomatincomplex |