7ZKW

Crystal structure of cystinosin from Arabidopsis thaliana in complex with Cystine and sybody

7ZKW の概要

• エントリーDOI: 10.2210/pdb7zkw/pdb
• 分子名称: Cystinosin homolog, sybody, L-cystine (3 entities in total)
• 機能のキーワード: cystinosin; pq-loop protein; proton coupling; cystine transport, membrane protein
• 由来する生物種: Arabidopsis thaliana (thale cress); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 91588.65

構造登録者

Parker, J.L.,Loebel, M.,Newstead, S. (登録日: 2022-04-13, 公開日: 2022-08-31, 最終更新日: 2024-11-06)

主引用文献

Lobel, M.,Salphati, S.P.,El Omari, K.,Wagner, A.,Tucker, S.J.,Parker, J.L.,Newstead, S.
Structural basis for proton coupled cystine transport by cystinosin.
Nat Commun, 13:4845-4845, 2022

PubMed Abstract: 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.

PubMed: 35977944
DOI: 10.1038/s41467-022-32589-2

実験手法

X-RAY DIFFRACTION (3.372 Å)