6MP6

Cryo-EM structure of the human neutral amino acid transporter ASCT2


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.54 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Cryo-EM structures of the human glutamine transporter SLC1A5 (ASCT2) in the outward-facing conformation.

Yu, X.Plotnikova, O.Bonin, P.D.Subashi, T.A.McLellan, T.J.Dumlao, D.Che, Y.Dong, Y.Y.Carpenter, E.P.West, G.M.Qiu, X.Culp, J.S.Han, S.

(2019) Elife 8

  • DOI: https://doi.org/10.7554/eLife.48120
  • Primary Citation of Related Structures:  
    6MP6, 6MPB

  • PubMed Abstract: 

    Alanine-serine-cysteine transporter 2 (ASCT2, SLC1A5) is the primary transporter of glutamine in cancer cells and regulates the mTORC1 signaling pathway. The SLC1A5 function involves finely tuned orchestration of two domain movements that include the substrate-binding transport domain and the scaffold domain. Here, we present cryo-EM structures of human SLC1A5 and its complex with the substrate, L-glutamine in an outward-facing conformation. These structures reveal insights into the conformation of the critical ECL2a loop which connects the two domains, thus allowing rigid body movement of the transport domain throughout the transport cycle. Furthermore, the structures provide new insights into substrate recognition, which involves conformational changes in the HP2 loop. A putative cholesterol binding site was observed near the domain interface in the outward-facing state. Comparison with the previously determined inward-facing structure of SCL1A5 provides a basis for a more integrated understanding of substrate recognition and transport mechanism in the SLC1 family.


  • Organizational Affiliation

    Medicine Design, Pfizer Inc, Groton, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Neutral amino acid transporter B(0)
A, B, C
541Homo sapiensMutation(s): 0 
Gene Names: SLC1A5ASCT2M7V1RDRRDRC
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for Q15758 (Homo sapiens)
Explore Q15758 
Go to UniProtKB:  Q15758
PHAROS:  Q15758
GTEx:  ENSG00000105281 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15758
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.54 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONcisTEM
MODEL REFINEMENTPHENIX

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2019-11-06 
  • Deposition Author(s): Yu, X., Han, S.

Revision History  (Full details and data files)

  • Version 1.0: 2019-11-06
    Type: Initial release
  • Version 1.1: 2019-11-27
    Changes: Data collection
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary