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A structural view onto disease-linked mutations in the human neutral amino acid exchanger ASCT1

Comput Struct Biotechnol J. 2021-09; 
Pavlo Stehantsev, Artem Stetsenko, Mariia Nemchinova, Nanda Gowtham Aduri, Siewert J Marrink, Cornelius Gati, Albert Guskov
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Mammalian Expression The pPICZ-B vector with incorporated human wild-type ASCT1 gene was ordered from GenScript. Get A Quote

摘要

The ASCT1 transporter of the SLC1 family is largely involved in equilibration of neutral amino acids' pools across the plasma membrane and plays a prominent role in the transport of both L- and D-isomers of serine, essential for the normal functioning of the central nervous system in mammals. A number of mutations in ASCT1 (E256K, G381R, R457W) have been linked to severe neurodevelopmental disorders, however in the absence of ASCT1 structure it is hard to understand their impact on substrate transport. To ameliorate that we have determined a cryo-EM structure of human ASCT1 at 4.2 Å resolution and performed functional transport assays and molecular dynamics simulations, which revealed that given mutations lea... More

关键词

ASCT1, Cryo-EM, Membrane transporter, Molecular dynamics, Solute carrier, Structural biology