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Structural basis of substrate recognition and translocation by human ABCA4

Nature Communications. 2021-06; 
Tian Xie, Zike Zhang, Qi Fang, Bowen Du& Xin Gong
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摘要

Human ATP-binding cassette (ABC) subfamily A (ABCA) transporters mediate the transport of various lipid compounds across the membrane. Mutations in human ABCA transporters have been described to cause severe hereditary disorders associated with impaired lipid transport. However, little is known about the mechanistic details of substrate recognition and translocation by ABCA transporters. Here, we present three cryo-EM structures of human ABCA4, a retina-speci?c ABCA transporter, in distinct functional states at resolutions of 3.3–3.4 A?. In the nucleotide-free state, the two transmembrane domains (TMDs) exhibit a lateral-opening conformation, allowing the lateral entry of substrate from the lipid bilayer. ... More

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