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TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells

TMEM120A, a member of the transmembrane protein 120 (TMEM120) family, has a pivotal function in adipocyte differentiation and metabolism, and may also contribute to sensing mechanical pain by functioning as an ion channel named TACAN. Here we report that expression of TMEM120A is not sufficient in m...

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Autores principales: Rong, Yao, Jiang, Jinghui, Gao, Yiwei, Guo, Jianli, Song, Danfeng, Liu, Wenhao, Zhang, Mingmin, Zhao, Yan, Xiao, Bailong, Liu, Zhenfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480983/
https://www.ncbi.nlm.nih.gov/pubmed/34409941
http://dx.doi.org/10.7554/eLife.71474
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author Rong, Yao
Jiang, Jinghui
Gao, Yiwei
Guo, Jianli
Song, Danfeng
Liu, Wenhao
Zhang, Mingmin
Zhao, Yan
Xiao, Bailong
Liu, Zhenfeng
author_facet Rong, Yao
Jiang, Jinghui
Gao, Yiwei
Guo, Jianli
Song, Danfeng
Liu, Wenhao
Zhang, Mingmin
Zhao, Yan
Xiao, Bailong
Liu, Zhenfeng
author_sort Rong, Yao
collection PubMed
description TMEM120A, a member of the transmembrane protein 120 (TMEM120) family, has a pivotal function in adipocyte differentiation and metabolism, and may also contribute to sensing mechanical pain by functioning as an ion channel named TACAN. Here we report that expression of TMEM120A is not sufficient in mediating poking- or stretch-induced currents in cells and have solved cryo-electron microscopy (cryo-EM) structures of human TMEM120A (HsTMEM120A) in complex with an endogenous metabolic cofactor (coenzyme A, CoASH) and in the apo form. HsTMEM120A forms a symmetrical homodimer with each monomer containing an amino-terminal coiled-coil motif followed by a transmembrane domain with six membrane-spanning helices. Within the transmembrane domain, a CoASH molecule is hosted in a deep cavity and forms specific interactions with nearby amino acid residues. Mutation of a central tryptophan residue involved in binding CoASH dramatically reduced the binding affinity of HsTMEM120A with CoASH. HsTMEM120A exhibits distinct conformations at the states with or without CoASH bound. Our results suggest that TMEM120A may have alternative functional roles potentially involved in CoASH transport, sensing, or metabolism.
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spelling pubmed-84809832021-09-30 TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells Rong, Yao Jiang, Jinghui Gao, Yiwei Guo, Jianli Song, Danfeng Liu, Wenhao Zhang, Mingmin Zhao, Yan Xiao, Bailong Liu, Zhenfeng eLife Neuroscience TMEM120A, a member of the transmembrane protein 120 (TMEM120) family, has a pivotal function in adipocyte differentiation and metabolism, and may also contribute to sensing mechanical pain by functioning as an ion channel named TACAN. Here we report that expression of TMEM120A is not sufficient in mediating poking- or stretch-induced currents in cells and have solved cryo-electron microscopy (cryo-EM) structures of human TMEM120A (HsTMEM120A) in complex with an endogenous metabolic cofactor (coenzyme A, CoASH) and in the apo form. HsTMEM120A forms a symmetrical homodimer with each monomer containing an amino-terminal coiled-coil motif followed by a transmembrane domain with six membrane-spanning helices. Within the transmembrane domain, a CoASH molecule is hosted in a deep cavity and forms specific interactions with nearby amino acid residues. Mutation of a central tryptophan residue involved in binding CoASH dramatically reduced the binding affinity of HsTMEM120A with CoASH. HsTMEM120A exhibits distinct conformations at the states with or without CoASH bound. Our results suggest that TMEM120A may have alternative functional roles potentially involved in CoASH transport, sensing, or metabolism. eLife Sciences Publications, Ltd 2021-08-19 /pmc/articles/PMC8480983/ /pubmed/34409941 http://dx.doi.org/10.7554/eLife.71474 Text en © 2021, Rong et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Rong, Yao
Jiang, Jinghui
Gao, Yiwei
Guo, Jianli
Song, Danfeng
Liu, Wenhao
Zhang, Mingmin
Zhao, Yan
Xiao, Bailong
Liu, Zhenfeng
TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells
title TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells
title_full TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells
title_fullStr TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells
title_full_unstemmed TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells
title_short TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells
title_sort tmem120a contains a specific coenzyme a-binding site and might not mediate poking- or stretch-induced channel activities in cells
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480983/
https://www.ncbi.nlm.nih.gov/pubmed/34409941
http://dx.doi.org/10.7554/eLife.71474
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