4p60

Structure of the N-terminal domain of the human mitochondrial aspartate/glutamate carrier Aralar in the apo state

spinqualitylabelsall models 4p60, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p60 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NA Related: 4p5x Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [CMC1_HUMAN] Epileptic encephalopathy with global cerebral demyelination. The disease is caused by mutations affecting the gene represented in this entry. Function [CMC1_HUMAN] Catalyzes the calcium-dependent exchange of cytoplasmic glutamate with mitochondrial aspartate across the mitochondrial inner membrane. May have a function in the urea cycle. Publication Abstract from PubMed 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. Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers.,Thangaratnarajah C, Ruprecht JJ, Kunji ER Nat Commun. 2014 Nov 20;5:5491. doi: 10.1038/ncomms6491. PMID:25410934 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA