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- PDB-7n7p: Cryo-EM structure of human TMEM120A -

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Basic information

Entry
Database: PDB / ID: 7n7p
TitleCryo-EM structure of human TMEM120A
ComponentsIon channel TACAN
KeywordsMEMBRANE PROTEIN / Transmembrane protein
Function / homology
Function and homology information


protein heterooligomerization / nuclear inner membrane / fat cell differentiation / detection of mechanical stimulus involved in sensory perception of pain / monoatomic ion transmembrane transport / protein homooligomerization / monoatomic ion channel activity / membrane / plasma membrane
Similarity search - Function
Ion channel TACAN/TMEM120B / TMPIT-like protein
Similarity search - Domain/homology
COENZYME A / Ion channel TACAN
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.24 Å
AuthorsXue, J. / Han, Y. / Jiang, Y.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM079179 United States
CitationJournal: Elife / Year: 2021
Title: TMEM120A is a coenzyme A-binding membrane protein with structural similarities to ELOVL fatty acid elongase.
Authors: Jing Xue / Yan Han / Hamid Baniasadi / Weizhong Zeng / Jimin Pei / Nick V Grishin / Junmei Wang / Benjamin P Tu / Youxing Jiang /
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 ...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 α-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.
History
DepositionJun 10, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 1, 2021Provider: repository / Type: Initial release

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Structure visualization

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Assembly

Deposited unit
A: Ion channel TACAN
B: Ion channel TACAN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)85,5624
Polymers84,0272
Non-polymers1,5352
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Ion channel TACAN / Transmembrane protein 120A / TMEM120A / Transmembrane protein induced by tumor necrosis factor alpha


Mass: 42013.457 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TMEM120A, TACAN, TMPIT / Production host: Homo sapiens (human) / References: UniProt: Q9BXJ8
#2: Chemical ChemComp-COA / COENZYME A / Coenzyme A


Mass: 767.534 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H36N7O16P3S / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Human TMEM120A with CoA / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 1 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING ONLY
3D reconstructionResolution: 3.24 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 701283 / Symmetry type: POINT

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