Tmem120a is a coenzyme a-binding membrane protein with structural similarities to elovl fatty acid elongase

Jing Xue; Yan Han; Hamid Baniasadi; Weizhong Zeng; Jimin Pei; Nick V. Grishin; Junmei Wang; Benjamin P. Tu; Youxing Jiang

doi:10.7554/ELIFE.71220

Tmem120a is a coenzyme a-binding membrane protein with structural similarities to elovl fatty acid elongase

Jing Xue, Yan Han, Hamid Baniasadi, Weizhong Zeng, Jimin Pei, Nick V. Grishin, Junmei Wang, Benjamin P. Tu, Youxing Jiang

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

TMEM120A, also named as TACAN, is a novel membrane protein highly conserved in vertebrates and was recently proposed to be a mechanosensitive channel involved in sensing mechanical pain. Here we present the single-particle cryogenic electron microscopy (cryo-EM) structure of human TMEM120A, which forms a tightly packed dimer with extensive interactions mediated by the N-terminal coiled coil domain (CCD), the C-terminal transmembrane domain (TMD), and the re-entrant loop between the two domains. The TMD of each TMEM120A subunit contains six transmembrane helices (TMs) and has no clear structural feature of a channel protein. Instead, the six TMs form an a-barrel with a deep pocket where a coenzyme A (CoA) molecule is bound. Intriguingly, some structural features of TMEM120A resemble those of elongase for very long-chain fatty acids (ELOVL) despite the low sequence homology between them, pointing to the possibility that TMEM120A may function as an enzyme for fatty acid metabolism, rather than a mechanosensitive channel.

Original language	English (US)
Article number	e71220
Journal	eLife
Volume	10
DOIs	https://doi.org/10.7554/ELIFE.71220
State	Published - 2021

ASJC Scopus subject areas

Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

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10.7554/ELIFE.71220

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@article{9626518db2164f8badd608bbe5606beb,

title = "Tmem120a is a coenzyme a-binding membrane protein with structural similarities to elovl fatty acid elongase",

abstract = "TMEM120A, also named as TACAN, is a novel membrane protein highly conserved in vertebrates and was recently proposed to be a mechanosensitive channel involved in sensing mechanical pain. Here we present the single-particle cryogenic electron microscopy (cryo-EM) structure of human TMEM120A, which forms a tightly packed dimer with extensive interactions mediated by the N-terminal coiled coil domain (CCD), the C-terminal transmembrane domain (TMD), and the re-entrant loop between the two domains. The TMD of each TMEM120A subunit contains six transmembrane helices (TMs) and has no clear structural feature of a channel protein. Instead, the six TMs form an a-barrel with a deep pocket where a coenzyme A (CoA) molecule is bound. Intriguingly, some structural features of TMEM120A resemble those of elongase for very long-chain fatty acids (ELOVL) despite the low sequence homology between them, pointing to the possibility that TMEM120A may function as an enzyme for fatty acid metabolism, rather than a mechanosensitive channel.",

author = "Jing Xue and Yan Han and Hamid Baniasadi and Weizhong Zeng and Jimin Pei and Grishin, {Nick V.} and Junmei Wang and Tu, {Benjamin P.} and Youxing Jiang",

note = "Funding Information: Single-particle cryo-EM data were collected at the University of Texas Southwestern Medical Center Cryo-EM Facility that is funded by the CPRIT Core Facility Support Award RP170644 and the Howard Hughes Medical Institute Janelia Cryo-EM Facility. We thank Rui Yan at the Janelia Cryo-EM Facility for help in microscope operation and data collection. We thank Dr. A Patapoutian (HHMI/Scripps Research Institute) for providing the Piezo1 knockout HEK293 cells. This work was supported in part by the Howard Hughes Medical Institute (YJ and NVG) and by grants from the National Institute of Health (R35GM140892 to YJ, R35GM136370 to BPT, and GM127390 to NVG), the Welch Foundation (Grant I-1578 to YJ and I-1505 to NVG), and the National Science Foundation (1955260 to JW). Publisher Copyright: {\textcopyright} Xue et al.",

year = "2021",

doi = "10.7554/ELIFE.71220",

language = "English (US)",

volume = "10",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

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T1 - Tmem120a is a coenzyme a-binding membrane protein with structural similarities to elovl fatty acid elongase

AU - Xue, Jing

AU - Han, Yan

AU - Baniasadi, Hamid

AU - Zeng, Weizhong

AU - Pei, Jimin

AU - Grishin, Nick V.

AU - Wang, Junmei

AU - Tu, Benjamin P.

AU - Jiang, Youxing

N1 - Funding Information: Single-particle cryo-EM data were collected at the University of Texas Southwestern Medical Center Cryo-EM Facility that is funded by the CPRIT Core Facility Support Award RP170644 and the Howard Hughes Medical Institute Janelia Cryo-EM Facility. We thank Rui Yan at the Janelia Cryo-EM Facility for help in microscope operation and data collection. We thank Dr. A Patapoutian (HHMI/Scripps Research Institute) for providing the Piezo1 knockout HEK293 cells. This work was supported in part by the Howard Hughes Medical Institute (YJ and NVG) and by grants from the National Institute of Health (R35GM140892 to YJ, R35GM136370 to BPT, and GM127390 to NVG), the Welch Foundation (Grant I-1578 to YJ and I-1505 to NVG), and the National Science Foundation (1955260 to JW). Publisher Copyright: © Xue et al.

PY - 2021

Y1 - 2021

N2 - TMEM120A, also named as TACAN, is a novel membrane protein highly conserved in vertebrates and was recently proposed to be a mechanosensitive channel involved in sensing mechanical pain. Here we present the single-particle cryogenic electron microscopy (cryo-EM) structure of human TMEM120A, which forms a tightly packed dimer with extensive interactions mediated by the N-terminal coiled coil domain (CCD), the C-terminal transmembrane domain (TMD), and the re-entrant loop between the two domains. The TMD of each TMEM120A subunit contains six transmembrane helices (TMs) and has no clear structural feature of a channel protein. Instead, the six TMs form an a-barrel with a deep pocket where a coenzyme A (CoA) molecule is bound. Intriguingly, some structural features of TMEM120A resemble those of elongase for very long-chain fatty acids (ELOVL) despite the low sequence homology between them, pointing to the possibility that TMEM120A may function as an enzyme for fatty acid metabolism, rather than a mechanosensitive channel.

AB - TMEM120A, also named as TACAN, is a novel membrane protein highly conserved in vertebrates and was recently proposed to be a mechanosensitive channel involved in sensing mechanical pain. Here we present the single-particle cryogenic electron microscopy (cryo-EM) structure of human TMEM120A, which forms a tightly packed dimer with extensive interactions mediated by the N-terminal coiled coil domain (CCD), the C-terminal transmembrane domain (TMD), and the re-entrant loop between the two domains. The TMD of each TMEM120A subunit contains six transmembrane helices (TMs) and has no clear structural feature of a channel protein. Instead, the six TMs form an a-barrel with a deep pocket where a coenzyme A (CoA) molecule is bound. Intriguingly, some structural features of TMEM120A resemble those of elongase for very long-chain fatty acids (ELOVL) despite the low sequence homology between them, pointing to the possibility that TMEM120A may function as an enzyme for fatty acid metabolism, rather than a mechanosensitive channel.

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DO - 10.7554/ELIFE.71220

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AN - SCOPUS:85113180234

SN - 2050-084X

VL - 10

JO - eLife

JF - eLife

M1 - e71220

ER -

Tmem120a is a coenzyme a-binding membrane protein with structural similarities to elovl fatty acid elongase

Abstract

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