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Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining
Vacuolar-type adenosine triphosphatases (V-ATPases) not only function as rotary proton pumps in cellular organelles but also serve as signaling hubs. To identify the endogenous binding partners of V-ATPase, we collected a large dataset of human V-ATPases and did extensive classification and focused...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436323/ https://www.ncbi.nlm.nih.gov/pubmed/35994636 http://dx.doi.org/10.1073/pnas.2203742119 |
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author | Wang, Longfei Wu, Di Robinson, Carol V. Fu, Tian-Min |
author_facet | Wang, Longfei Wu, Di Robinson, Carol V. Fu, Tian-Min |
author_sort | Wang, Longfei |
collection | PubMed |
description | Vacuolar-type adenosine triphosphatases (V-ATPases) not only function as rotary proton pumps in cellular organelles but also serve as signaling hubs. To identify the endogenous binding partners of V-ATPase, we collected a large dataset of human V-ATPases and did extensive classification and focused refinement of human V-ATPases. Unexpectedly, about 17% of particles in state 2 of human V-ATPases display additional density with an overall resolution of 3.3 Å. Structural analysis combined with artificial intelligence modeling enables us to identify this additional density as mEAK-7, a protein involved in mechanistic target of rapamycin (mTOR) signaling in mammals. Our structure shows that mEAK-7 interacts with subunits A, B, D, and E of V-ATPases in state 2. Thus, we propose that mEAK-7 may regulate V-ATPase function through binding to V-ATPases in state 2 as well as mediate mTOR signaling. |
format | Online Article Text |
id | pubmed-9436323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-94363232022-09-02 Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining Wang, Longfei Wu, Di Robinson, Carol V. Fu, Tian-Min Proc Natl Acad Sci U S A Biological Sciences Vacuolar-type adenosine triphosphatases (V-ATPases) not only function as rotary proton pumps in cellular organelles but also serve as signaling hubs. To identify the endogenous binding partners of V-ATPase, we collected a large dataset of human V-ATPases and did extensive classification and focused refinement of human V-ATPases. Unexpectedly, about 17% of particles in state 2 of human V-ATPases display additional density with an overall resolution of 3.3 Å. Structural analysis combined with artificial intelligence modeling enables us to identify this additional density as mEAK-7, a protein involved in mechanistic target of rapamycin (mTOR) signaling in mammals. Our structure shows that mEAK-7 interacts with subunits A, B, D, and E of V-ATPases in state 2. Thus, we propose that mEAK-7 may regulate V-ATPase function through binding to V-ATPases in state 2 as well as mediate mTOR signaling. National Academy of Sciences 2022-08-22 2022-08-30 /pmc/articles/PMC9436323/ /pubmed/35994636 http://dx.doi.org/10.1073/pnas.2203742119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Wang, Longfei Wu, Di Robinson, Carol V. Fu, Tian-Min Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining |
title | Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining |
title_full | Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining |
title_fullStr | Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining |
title_full_unstemmed | Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining |
title_short | Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining |
title_sort | identification of meak-7 as a human v-atpase regulator via cryo-em data mining |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436323/ https://www.ncbi.nlm.nih.gov/pubmed/35994636 http://dx.doi.org/10.1073/pnas.2203742119 |
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