PDBsum entry 4p60

Transport protein

PDB id: 4p60

Contents

Protein chains

239 a.a.

284 a.a.

Metals

_NA

Waters ×21

PDB id:

4p60

Name:

Transport protein

Title:

Structure of the n-terminal domain of the human mitochondrial aspartate/glutamate carrier aralar in the apo state

Structure:

Calcium-binding mitochondrial carrier protein aralar1. Chain: a, b. Fragment: residues 2-311. Synonym: mitochondrial aspartate glutamate carrier 1, solute carrier family 25 member 12. Engineered: yes. Other_details: n-terminal domain of aralar, apo-state

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: slc25a12, aralar1. Expressed in: lactococcus lactis subsp. Cremoris nz9000. Expression_system_taxid: 746361.

Resolution:

2.40Å R-factor: 0.248 R-free: 0.297

Authors:

C.Thangaratnarajah,J.J.Ruprecht,E.R.S.Kunji

Key ref:

C.Thangaratnarajah et al. (2014). Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. Nat Commun, 5, 5491. PubMed id: 25410934 DOI: 10.1038/ncomms6491

Date:

20-Mar-14 Release date: 26-Nov-14

Protein chain

O75746  (CMC1_HUMAN) -  Electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrial from Homo sapiens

Seq: 678 a.a.

Struc: 239 a.a.

Protein chain

O75746  (CMC1_HUMAN) -  Electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrial from Homo sapiens

Seq: 678 a.a.

Struc: 284 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1038/ncomms6491

Nat Commun 5:5491 (2014)

PubMed id: 25410934

Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers.

C.Thangaratnarajah, J.J.Ruprecht, E.R.Kunji.

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.