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Cryo-EM structure of the Mon1–Ccz1–RMC1 complex reveals molecular basis of metazoan RAB7A activation
Understanding of the evolution of metazoans from their unicellular ancestors is a fundamental question in biology. In contrast to fungi which utilize the Mon1–Ccz1 dimeric complex to activate the small GTPase RAB7A, metazoans rely on the Mon1–Ccz1–RMC1 trimeric complex. Here, we report a near-atomic...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235969/ https://www.ncbi.nlm.nih.gov/pubmed/37216550 http://dx.doi.org/10.1073/pnas.2301725120 |
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author | Yong, Xin Jia, Guowen Liu, Zhe Zhou, Chunzhuang Yi, Jiamin Tang, Yingying Chen, Li Chen, Lu Wang, Yuan Sun, Qingxiang Billadeau, Daniel D. Su, Zhaoming Jia, Da |
author_facet | Yong, Xin Jia, Guowen Liu, Zhe Zhou, Chunzhuang Yi, Jiamin Tang, Yingying Chen, Li Chen, Lu Wang, Yuan Sun, Qingxiang Billadeau, Daniel D. Su, Zhaoming Jia, Da |
author_sort | Yong, Xin |
collection | PubMed |
description | Understanding of the evolution of metazoans from their unicellular ancestors is a fundamental question in biology. In contrast to fungi which utilize the Mon1–Ccz1 dimeric complex to activate the small GTPase RAB7A, metazoans rely on the Mon1–Ccz1–RMC1 trimeric complex. Here, we report a near-atomic resolution cryogenic-electron microscopy structure of the Drosophila Mon1–Ccz1–RMC1 complex. RMC1 acts as a scaffolding subunit and binds to both Mon1 and Ccz1 on the surface opposite to the RAB7A-binding site, with many of the RMC1-contacting residues from Mon1 and Ccz1 unique to metazoans, explaining the binding specificity. Significantly, the assembly of RMC1 with Mon1–Ccz1 is required for cellular RAB7A activation, autophagic functions and organismal development in zebrafish. Our studies offer a molecular explanation for the different degree of subunit conservation across species, and provide an excellent example of how metazoan-specific proteins take over existing functions in unicellular organisms. |
format | Online Article Text |
id | pubmed-10235969 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-102359692023-11-22 Cryo-EM structure of the Mon1–Ccz1–RMC1 complex reveals molecular basis of metazoan RAB7A activation Yong, Xin Jia, Guowen Liu, Zhe Zhou, Chunzhuang Yi, Jiamin Tang, Yingying Chen, Li Chen, Lu Wang, Yuan Sun, Qingxiang Billadeau, Daniel D. Su, Zhaoming Jia, Da Proc Natl Acad Sci U S A Biological Sciences Understanding of the evolution of metazoans from their unicellular ancestors is a fundamental question in biology. In contrast to fungi which utilize the Mon1–Ccz1 dimeric complex to activate the small GTPase RAB7A, metazoans rely on the Mon1–Ccz1–RMC1 trimeric complex. Here, we report a near-atomic resolution cryogenic-electron microscopy structure of the Drosophila Mon1–Ccz1–RMC1 complex. RMC1 acts as a scaffolding subunit and binds to both Mon1 and Ccz1 on the surface opposite to the RAB7A-binding site, with many of the RMC1-contacting residues from Mon1 and Ccz1 unique to metazoans, explaining the binding specificity. Significantly, the assembly of RMC1 with Mon1–Ccz1 is required for cellular RAB7A activation, autophagic functions and organismal development in zebrafish. Our studies offer a molecular explanation for the different degree of subunit conservation across species, and provide an excellent example of how metazoan-specific proteins take over existing functions in unicellular organisms. National Academy of Sciences 2023-05-22 2023-05-30 /pmc/articles/PMC10235969/ /pubmed/37216550 http://dx.doi.org/10.1073/pnas.2301725120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This 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 Yong, Xin Jia, Guowen Liu, Zhe Zhou, Chunzhuang Yi, Jiamin Tang, Yingying Chen, Li Chen, Lu Wang, Yuan Sun, Qingxiang Billadeau, Daniel D. Su, Zhaoming Jia, Da Cryo-EM structure of the Mon1–Ccz1–RMC1 complex reveals molecular basis of metazoan RAB7A activation |
title | Cryo-EM structure of the Mon1–Ccz1–RMC1 complex reveals molecular basis of metazoan RAB7A activation |
title_full | Cryo-EM structure of the Mon1–Ccz1–RMC1 complex reveals molecular basis of metazoan RAB7A activation |
title_fullStr | Cryo-EM structure of the Mon1–Ccz1–RMC1 complex reveals molecular basis of metazoan RAB7A activation |
title_full_unstemmed | Cryo-EM structure of the Mon1–Ccz1–RMC1 complex reveals molecular basis of metazoan RAB7A activation |
title_short | Cryo-EM structure of the Mon1–Ccz1–RMC1 complex reveals molecular basis of metazoan RAB7A activation |
title_sort | cryo-em structure of the mon1–ccz1–rmc1 complex reveals molecular basis of metazoan rab7a activation |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235969/ https://www.ncbi.nlm.nih.gov/pubmed/37216550 http://dx.doi.org/10.1073/pnas.2301725120 |
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