4P5W

Structure of the N- and C-terminal domain fusion of the human mitochondrial aspartate/glutamate carrier Citrin in the calcium-bound state

4P5W の概要

• エントリーDOI: 10.2210/pdb4p5w/pdb
• 分子名称: Calcium-binding mitochondrial carrier protein Aralar2,Calcium-binding mitochondrial carrier protein Aralar2, CALCIUM ION (3 entities in total)
• 機能のキーワード: transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Mitochondrion inner membrane ; Multi-pass membrane protein : Q9UJS0
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92040.34

構造登録者

Thangaratnarajah, C.,Ruprecht, J.J.,Kunji, E.R.S. (登録日: 2014-03-20, 公開日: 2014-11-26, 最終更新日: 2024-05-08)

主引用文献

Thangaratnarajah, C.,Ruprecht, J.J.,Kunji, E.R.
Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers.
Nat Commun, 5:5491-5491, 2014

PubMed Abstract: The transport activity of human mitochondrial aspartate/glutamate carriers is central to the malate-aspartate shuttle, urea cycle, gluconeogenesis and myelin synthesis. They have a unique three-domain structure, comprising a calcium-regulated N-terminal domain with eight EF-hands, a mitochondrial carrier domain, and a C-terminal domain. Here we present the calcium-bound and calcium-free structures of the N- and C-terminal domains, elucidating the mechanism of calcium regulation. Unexpectedly, EF-hands 4-8 are involved in dimerization of the carrier and form a static unit, whereas EF-hands 1-3 form a calcium-responsive mobile unit. On calcium binding, an amphipathic helix of the C-terminal domain binds to the N-terminal domain, opening a vestibule. In the absence of calcium, the mobile unit closes the vestibule. Opening and closing of the vestibule might regulate access of substrates to the carrier domain, which is involved in their transport. These structures provide a framework for understanding cases of the mitochondrial disease citrin deficiency.

PubMed: 25410934
DOI: 10.1038/ncomms6491

実験手法

X-RAY DIFFRACTION (2.4 Å)