Journal article
Structural basis for proton coupled cystine transport by cystinosin
- Abstract:
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Amino acid transporters play a key role controlling the flow of nutrients across the lysosomal membrane and regulating metabolism in the cell. Mutations in the gene encoding the transporter cystinosin result in cystinosis, an autosomal recessive metabolic disorder characterised by the accumulation of cystine crystals in the lysosome. Cystinosin is a member of the PQ-loop family of solute carrier (SLC) transporters and uses the proton gradient to drive cystine export into the cytoplasm. However, the molecular basis for cystinosin function remains elusive, hampering efforts to develop novel treatments for cystinosis and understand the mechanisms of ion driven transport in the PQ-loop family. To address these questions, we present the crystal structures of cystinosin from Arabidopsis thaliana in both apo and cystine bound states. Using a combination of in vitro and in vivo based assays, we establish a mechanism for cystine recognition and proton coupled transport. Mutational mapping and functional characterisation of human cystinosin further provide a framework for understanding the molecular impact of disease-causing mutations.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 2.3MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-022-32589-2
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 13
- Issue:
- 1
- Article number:
- 4845
- Publication date:
- 2022-08-17
- Acceptance date:
- 2022-08-08
- DOI:
- EISSN:
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2041-1723
- ISSN:
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2041-1723
- Pmid:
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35977944
- Language:
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English
- Keywords:
- Pubs id:
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1274864
- Local pid:
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pubs:1274864
- Deposit date:
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2022-11-30
Terms of use
- Copyright holder:
- Löbel et al.
- Copyright date:
- 2022
- Rights statement:
- © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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