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-Structure paper
Title | A structural view onto disease-linked mutations in the human neutral amino acid exchanger ASCT1. |
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Journal, issue, pages | Comput Struct Biotechnol J, Vol. 19, Page 5246-5254, Year 2021 |
Publish date | Sep 17, 2021 |
Authors | Pavlo Stehantsev / Artem Stetsenko / Mariia Nemchinova / Nanda Gowtham Aduri / Siewert J Marrink / Cornelius Gati / Albert Guskov / |
PubMed Abstract | 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- ...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 lead to the diminished transport capability of ASCT1 caused by instability of transporter and impeded transport cycle. |
External links | Comput Struct Biotechnol J / PubMed:34630942 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.2 Å |
Structure data | EMDB-13193, PDB-7p4i: |
Source |
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Keywords | TRANSPORT PROTEIN / Solute carrier / membrane protein / amino acid transport |