The cryo-EM structure of the SNX-BAR Mvp1 tetramer
Sorting nexins (SNX) are a family of PX domain-containing proteins with pivotal roles in trafficking and signaling. SNX-BARs, which also have a curvature-generating Bin/Amphiphysin/Rvs (BAR) domain, have membrane-remodeling functions, particularly at the endosome. The minimal PX-BAR module is a dime...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Research
2020
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| _version_ | 1797103155427672064 |
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| author | Sun, D Varlakhanova, NV Tornabene, BA Ramachandran, R Zhang, P Ford, MGJ |
| author_facet | Sun, D Varlakhanova, NV Tornabene, BA Ramachandran, R Zhang, P Ford, MGJ |
| author_sort | Sun, D |
| collection | OXFORD |
| description | Sorting nexins (SNX) are a family of PX domain-containing proteins with pivotal roles in trafficking and signaling. SNX-BARs, which also have a curvature-generating Bin/Amphiphysin/Rvs (BAR) domain, have membrane-remodeling functions, particularly at the endosome. The minimal PX-BAR module is a dimer mediated by BAR-BAR interactions. Many SNX-BAR proteins, however, additionally have low-complexity N-terminal regions of unknown function. Here, we present the cryo-EM structure of the full-length SNX-BAR Mvp1, which is an autoinhibited tetramer. The tetramer is a dimer of dimers, wherein the membrane-interacting BAR surfaces are sequestered and the PX lipid-binding sites are occluded. The N-terminal low-complexity region of Mvp1 is essential for tetramerization. Mvp1 lacking its N-terminus is dimeric and exhibits enhanced membrane association. Membrane binding and remodeling by Mvp1 therefore requires unmasking of the PX and BAR domain lipid-interacting surfaces. This work reveals a tetrameric configuration of a SNX-BAR protein that provides critical insight into SNX-BAR function and regulation. |
| first_indexed | 2024-03-07T06:16:04Z |
| format | Journal article |
| id | oxford-uuid:f11de4fd-b56a-4117-816f-246afbe9d078 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:16:04Z |
| publishDate | 2020 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:f11de4fd-b56a-4117-816f-246afbe9d0782022-03-27T11:53:34ZThe cryo-EM structure of the SNX-BAR Mvp1 tetramerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f11de4fd-b56a-4117-816f-246afbe9d078EnglishSymplectic ElementsNature Research2020Sun, DVarlakhanova, NVTornabene, BARamachandran, RZhang, PFord, MGJSorting nexins (SNX) are a family of PX domain-containing proteins with pivotal roles in trafficking and signaling. SNX-BARs, which also have a curvature-generating Bin/Amphiphysin/Rvs (BAR) domain, have membrane-remodeling functions, particularly at the endosome. The minimal PX-BAR module is a dimer mediated by BAR-BAR interactions. Many SNX-BAR proteins, however, additionally have low-complexity N-terminal regions of unknown function. Here, we present the cryo-EM structure of the full-length SNX-BAR Mvp1, which is an autoinhibited tetramer. The tetramer is a dimer of dimers, wherein the membrane-interacting BAR surfaces are sequestered and the PX lipid-binding sites are occluded. The N-terminal low-complexity region of Mvp1 is essential for tetramerization. Mvp1 lacking its N-terminus is dimeric and exhibits enhanced membrane association. Membrane binding and remodeling by Mvp1 therefore requires unmasking of the PX and BAR domain lipid-interacting surfaces. This work reveals a tetrameric configuration of a SNX-BAR protein that provides critical insight into SNX-BAR function and regulation. |
| spellingShingle | Sun, D Varlakhanova, NV Tornabene, BA Ramachandran, R Zhang, P Ford, MGJ The cryo-EM structure of the SNX-BAR Mvp1 tetramer |
| title | The cryo-EM structure of the SNX-BAR Mvp1 tetramer |
| title_full | The cryo-EM structure of the SNX-BAR Mvp1 tetramer |
| title_fullStr | The cryo-EM structure of the SNX-BAR Mvp1 tetramer |
| title_full_unstemmed | The cryo-EM structure of the SNX-BAR Mvp1 tetramer |
| title_short | The cryo-EM structure of the SNX-BAR Mvp1 tetramer |
| title_sort | cryo em structure of the snx bar mvp1 tetramer |
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