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Structural basis of TRAPPIII‐mediated Rab1 activation
The GTPase Rab1 is a master regulator of the early secretory pathway and is critical for autophagy. Rab1 activation is controlled by its guanine nucleotide exchange factor, the multisubunit TRAPPIII complex. Here, we report the 3.7 Å cryo‐EM structure of the Saccharomyces cerevisiae TRAPPIII complex...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204860/ https://www.ncbi.nlm.nih.gov/pubmed/34018207 http://dx.doi.org/10.15252/embj.2020107607 |
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author | Joiner, Aaron MN Phillips, Ben P Yugandhar, Kumar Sanford, Ethan J Smolka, Marcus B Yu, Haiyuan Miller, Elizabeth A Fromme, J Christopher |
author_facet | Joiner, Aaron MN Phillips, Ben P Yugandhar, Kumar Sanford, Ethan J Smolka, Marcus B Yu, Haiyuan Miller, Elizabeth A Fromme, J Christopher |
author_sort | Joiner, Aaron MN |
collection | PubMed |
description | The GTPase Rab1 is a master regulator of the early secretory pathway and is critical for autophagy. Rab1 activation is controlled by its guanine nucleotide exchange factor, the multisubunit TRAPPIII complex. Here, we report the 3.7 Å cryo‐EM structure of the Saccharomyces cerevisiae TRAPPIII complex bound to its substrate Rab1/Ypt1. The structure reveals the binding site for the Rab1/Ypt1 hypervariable domain, leading to a model for how the complex interacts with membranes during the activation reaction. We determined that stable membrane binding by the TRAPPIII complex is required for robust activation of Rab1/Ypt1 in vitro and in vivo, and is mediated by a conserved amphipathic α‐helix within the regulatory Trs85 subunit. Our results show that the Trs85 subunit serves as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes. |
format | Online Article Text |
id | pubmed-8204860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82048602021-06-28 Structural basis of TRAPPIII‐mediated Rab1 activation Joiner, Aaron MN Phillips, Ben P Yugandhar, Kumar Sanford, Ethan J Smolka, Marcus B Yu, Haiyuan Miller, Elizabeth A Fromme, J Christopher EMBO J Articles The GTPase Rab1 is a master regulator of the early secretory pathway and is critical for autophagy. Rab1 activation is controlled by its guanine nucleotide exchange factor, the multisubunit TRAPPIII complex. Here, we report the 3.7 Å cryo‐EM structure of the Saccharomyces cerevisiae TRAPPIII complex bound to its substrate Rab1/Ypt1. The structure reveals the binding site for the Rab1/Ypt1 hypervariable domain, leading to a model for how the complex interacts with membranes during the activation reaction. We determined that stable membrane binding by the TRAPPIII complex is required for robust activation of Rab1/Ypt1 in vitro and in vivo, and is mediated by a conserved amphipathic α‐helix within the regulatory Trs85 subunit. Our results show that the Trs85 subunit serves as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes. John Wiley and Sons Inc. 2021-05-21 2021-06-15 /pmc/articles/PMC8204860/ /pubmed/34018207 http://dx.doi.org/10.15252/embj.2020107607 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Joiner, Aaron MN Phillips, Ben P Yugandhar, Kumar Sanford, Ethan J Smolka, Marcus B Yu, Haiyuan Miller, Elizabeth A Fromme, J Christopher Structural basis of TRAPPIII‐mediated Rab1 activation |
title | Structural basis of TRAPPIII‐mediated Rab1 activation |
title_full | Structural basis of TRAPPIII‐mediated Rab1 activation |
title_fullStr | Structural basis of TRAPPIII‐mediated Rab1 activation |
title_full_unstemmed | Structural basis of TRAPPIII‐mediated Rab1 activation |
title_short | Structural basis of TRAPPIII‐mediated Rab1 activation |
title_sort | structural basis of trappiii‐mediated rab1 activation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204860/ https://www.ncbi.nlm.nih.gov/pubmed/34018207 http://dx.doi.org/10.15252/embj.2020107607 |
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