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- PDB-7mjs: Single-Particle Cryo-EM Structure of Major Facilitator Superfamil... -
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Basic information
Entry | Database: PDB / ID: 7mjs | ||||||||||||||||||||||||
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Title | Single-Particle Cryo-EM Structure of Major Facilitator Superfamily Domain containing 2A in complex with LPC-18:3 | ||||||||||||||||||||||||
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![]() | LIPID TRANSPORT/IMMUNE SYSTEM / MFS transporters / lysolipids / blood-brain barrier / omega-3 fatty acids / LIPID TRANSPORT-IMMUNE SYSTEM complex | ||||||||||||||||||||||||
Function / homology | ![]() Synthesis of PC / lysophosphatidylcholine flippase activity / regulation of phosphatidylethanolamine metabolic process / regulation of phosphatidylserine metabolic process / oleate transmembrane transporter activity / regulation of phosphatidylcholine metabolic process / regulation of neuron projection arborization / retina morphogenesis in camera-type eye / photoreceptor cell morphogenesis / lysophospholipid translocation ...Synthesis of PC / lysophosphatidylcholine flippase activity / regulation of phosphatidylethanolamine metabolic process / regulation of phosphatidylserine metabolic process / oleate transmembrane transporter activity / regulation of phosphatidylcholine metabolic process / regulation of neuron projection arborization / retina morphogenesis in camera-type eye / photoreceptor cell morphogenesis / lysophospholipid translocation / lysophospholipid:sodium symporter activity / photoreceptor cell outer segment organization / lipid transport across blood-brain barrier / very-low-density lipoprotein particle assembly / negative regulation of fatty acid beta-oxidation / regulation of dendrite development / retinal pigment epithelium development / positive regulation of triglyceride biosynthetic process / : / establishment of blood-brain barrier / transcytosis / motor behavior / maintenance of blood-brain barrier / plasma membrane => GO:0005886 / carbohydrate transport / regulation of multicellular organism growth / energy homeostasis / cellular response to starvation / hippocampus development / cognition / positive regulation of cell growth Similarity search - Function | ||||||||||||||||||||||||
Biological species | Synthetic construct (others)![]() ![]() | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.03 Å | ||||||||||||||||||||||||
![]() | Cater, R.J. / Chua, G.L. / Erramilli, S.K. / Keener, J.E. / Choy, B.C. / Tokarz, P. / Chin, C.F. / Quek, D.Q.Y. / Kloss, B. / Pepe, J.G. ...Cater, R.J. / Chua, G.L. / Erramilli, S.K. / Keener, J.E. / Choy, B.C. / Tokarz, P. / Chin, C.F. / Quek, D.Q.Y. / Kloss, B. / Pepe, J.G. / Parisi, G. / Wong, B.H. / Clarke, O.B. / Marty, M.T. / Kossiakoff, A.A. / Khelashvili, G. / Silver, D.L. / Mancia, F. | ||||||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Structural basis of omega-3 fatty acid transport across the blood-brain barrier. Authors: Rosemary J Cater / Geok Lin Chua / Satchal K Erramilli / James E Keener / Brendon C Choy / Piotr Tokarz / Cheen Fei Chin / Debra Q Y Quek / Brian Kloss / Joseph G Pepe / Giacomo Parisi / ...Authors: Rosemary J Cater / Geok Lin Chua / Satchal K Erramilli / James E Keener / Brendon C Choy / Piotr Tokarz / Cheen Fei Chin / Debra Q Y Quek / Brian Kloss / Joseph G Pepe / Giacomo Parisi / Bernice H Wong / Oliver B Clarke / Michael T Marty / Anthony A Kossiakoff / George Khelashvili / David L Silver / Filippo Mancia / ![]() ![]() Abstract: Docosahexaenoic acid is an omega-3 fatty acid that is essential for neurological development and function, and it is supplied to the brain and eyes predominantly from dietary sources. This nutrient ...Docosahexaenoic acid is an omega-3 fatty acid that is essential for neurological development and function, and it is supplied to the brain and eyes predominantly from dietary sources. This nutrient is transported across the blood-brain and blood-retina barriers in the form of lysophosphatidylcholine by major facilitator superfamily domain containing 2A (MFSD2A) in a Na-dependent manner. Here we present the structure of MFSD2A determined using single-particle cryo-electron microscopy, which reveals twelve transmembrane helices that are separated into two pseudosymmetric domains. The transporter is in an inward-facing conformation and features a large amphipathic cavity that contains the Na-binding site and a bound lysolipid substrate, which we confirmed using native mass spectrometry. Together with our functional analyses and molecular dynamics simulations, this structure reveals details of how MFSD2A interacts with substrates and how Na-dependent conformational changes allow for the release of these substrates into the membrane through a lateral gate. Our work provides insights into the molecular mechanism by which this atypical major facility superfamily transporter mediates the uptake of lysolipids into the brain, and has the potential to aid in the delivery of neurotherapeutic agents. | ||||||||||||||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 135.1 KB | Display | ![]() |
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PDB format | ![]() | 107.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 40.1 KB | Display | |
Data in CIF | ![]() | 57.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 23883MC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 3.9 TB Data #1: MFSD2A_GG_compled with 2AG3 Fab and LPC-18:3 [micrographs - multiframe]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Antibody | Mass: 25646.537 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Synthetic construct (others) / Production host: ![]() ![]() | ||
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#2: Antibody | Mass: 23655.182 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Synthetic construct (others) / Production host: ![]() ![]() | ||
#3: Protein | Mass: 60789.168 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() | ||
#4: Chemical | ChemComp-ZGS / [( | ||
#5: Sugar | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Single-Particle Cryo-EM Structure of Major Facilitator Superfamily Domain containing 2A (MFSD2A) Gallus gallus in complex with LPC-18:3 Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Molecular weight | Units: MEGADALTONS / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Microscopy | Model: FEI TITAN |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Average exposure time: 3 sec. / Electron dose: 58 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
Image scans | Sampling size: 5 µm / Width: 5760 / Height: 4092 |
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Processing
CTF correction | Details: Patch CTF / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.03 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 175738 / Symmetry type: POINT |