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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
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.
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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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