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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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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. |
format | Online Article Text |
id | pubmed-8480983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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