7N98

Cryo-EM structure of MFSD2A

Summary for 7N98

• Entry DOI: 10.2210/pdb7n98/pdb
• EMDB information: 24252
• Descriptor: Sodium-dependent lysophosphatidylcholine symporter 1 (1 entity in total)
• Functional Keywords: membrane protein, transport protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 59038.60

Authors

Zhang, J.,Feng, L. (deposition date: 2021-06-17, release date: 2021-08-04, Last modification date: 2024-11-13)

Primary citation

Wood, C.A.P.,Zhang, J.,Aydin, D.,Xu, Y.,Andreone, B.J.,Langen, U.H.,Dror, R.O.,Gu, C.,Feng, L.
Structure and mechanism of blood-brain-barrier lipid transporter MFSD2A.
Nature, 596:444-448, 2021

PubMed Abstract: MFSD2A is a sodium-dependent lysophosphatidylcholine symporter that is responsible for the uptake of docosahexaenoic acid into the brain, which is crucial for the development and performance of the brain. Mutations that affect MFSD2A cause microcephaly syndromes. The ability of MFSD2A to transport lipid is also a key mechanism that underlies its function as an inhibitor of transcytosis to regulate the blood-brain barrier. Thus, MFSD2A represents an attractive target for modulating the permeability of the blood-brain barrier for drug delivery. Here we report the cryo-electron microscopy structure of mouse MFSD2A. Our structure defines the architecture of this important transporter, reveals its unique extracellular domain and uncovers its substrate-binding cavity. The structure-together with our functional studies and molecular dynamics simulations-identifies a conserved sodium-binding site, reveals a potential lipid entry pathway and helps to rationalize MFSD2A mutations that underlie microcephaly syndromes. These results shed light on the critical lipid transport function of MFSD2A and provide a framework to aid in the design of specific modulators for therapeutic purposes.

PubMed: 34349262
DOI: 10.1038/s41586-021-03782-y

Experimental method

ELECTRON MICROSCOPY (3.5 Å)