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Structural insights into the cooperative remodeling of membranes by amphiphysin/BIN1
Amphiphysin2/BIN1 is a crescent-shaped N-BAR protein playing a key role in forming deeply invaginated tubes in muscle T-tubules. Amphiphysin2/BIN1 structurally stabilizes tubular formations in contrast to other N-BAR proteins involved in dynamic membrane scission processes; however, the molecular me...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614383/ https://www.ncbi.nlm.nih.gov/pubmed/26487375 http://dx.doi.org/10.1038/srep15452 |
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author | Adam, Julia Basnet, Nirakar Mizuno, Naoko |
author_facet | Adam, Julia Basnet, Nirakar Mizuno, Naoko |
author_sort | Adam, Julia |
collection | PubMed |
description | Amphiphysin2/BIN1 is a crescent-shaped N-BAR protein playing a key role in forming deeply invaginated tubes in muscle T-tubules. Amphiphysin2/BIN1 structurally stabilizes tubular formations in contrast to other N-BAR proteins involved in dynamic membrane scission processes; however, the molecular mechanism of the stabilizing effect is poorly understood. Using cryo-EM, we investigated the assembly of the amphiphysin/BIN1 on a membrane tube. We found that the N-BAR domains self-assemble on the membrane surface in a highly cooperative manner. Our biochemical assays and 3D reconstructions indicate that the N-terminal amphipathic helix H0 plays an important role in the initiation of the tube assembly and further in organizing BAR-mediated polymerization by locking adjacent N-BAR domains. Mutants that lack H0 or the tip portion, which is also involved in interactions of the neighboring BAR unit, lead to a disruption of the polymer organization, even though tubulation can still be observed. The regulatory region of amphiphysin/BIN1 including an SH3 domain does not have any apparent involvement in the polymer lattice. Our study indicates that the H0 helix and the BAR tip are necessary for efficient and organized self-assembly of amphiphysin/N-BAR. |
format | Online Article Text |
id | pubmed-4614383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46143832015-10-29 Structural insights into the cooperative remodeling of membranes by amphiphysin/BIN1 Adam, Julia Basnet, Nirakar Mizuno, Naoko Sci Rep Article Amphiphysin2/BIN1 is a crescent-shaped N-BAR protein playing a key role in forming deeply invaginated tubes in muscle T-tubules. Amphiphysin2/BIN1 structurally stabilizes tubular formations in contrast to other N-BAR proteins involved in dynamic membrane scission processes; however, the molecular mechanism of the stabilizing effect is poorly understood. Using cryo-EM, we investigated the assembly of the amphiphysin/BIN1 on a membrane tube. We found that the N-BAR domains self-assemble on the membrane surface in a highly cooperative manner. Our biochemical assays and 3D reconstructions indicate that the N-terminal amphipathic helix H0 plays an important role in the initiation of the tube assembly and further in organizing BAR-mediated polymerization by locking adjacent N-BAR domains. Mutants that lack H0 or the tip portion, which is also involved in interactions of the neighboring BAR unit, lead to a disruption of the polymer organization, even though tubulation can still be observed. The regulatory region of amphiphysin/BIN1 including an SH3 domain does not have any apparent involvement in the polymer lattice. Our study indicates that the H0 helix and the BAR tip are necessary for efficient and organized self-assembly of amphiphysin/N-BAR. Nature Publishing Group 2015-10-21 /pmc/articles/PMC4614383/ /pubmed/26487375 http://dx.doi.org/10.1038/srep15452 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Adam, Julia Basnet, Nirakar Mizuno, Naoko Structural insights into the cooperative remodeling of membranes by amphiphysin/BIN1 |
title | Structural insights into the cooperative remodeling of membranes by amphiphysin/BIN1 |
title_full | Structural insights into the cooperative remodeling of membranes by amphiphysin/BIN1 |
title_fullStr | Structural insights into the cooperative remodeling of membranes by amphiphysin/BIN1 |
title_full_unstemmed | Structural insights into the cooperative remodeling of membranes by amphiphysin/BIN1 |
title_short | Structural insights into the cooperative remodeling of membranes by amphiphysin/BIN1 |
title_sort | structural insights into the cooperative remodeling of membranes by amphiphysin/bin1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614383/ https://www.ncbi.nlm.nih.gov/pubmed/26487375 http://dx.doi.org/10.1038/srep15452 |
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