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Calcium-induced conformational changes in the regulatory domain of the human mitochondrial ATP-Mg/Pi carrier.

Harborne SP, Ruprecht JJ, Kunji ER - Biochim. Biophys. Acta (2015)

Bottom Line: Careful analysis by SEC confirmed that although the regulatory domain crystallised as dimers, full-length ATP-Mg/Pi carrier is monomeric.Detailed bioinformatics analyses of different EF-hand states indicate that upon release of calcium, EF-hands close, meaning that the regulatory domain would release the amphipathic α-helix.We propose a mechanism for ATP-Mg/Pi carriers in which the amphipathic α-helix becomes mobile upon release of calcium and could block the transport of substrates across the mitochondrial inner membrane.

View Article: PubMed Central - PubMed

Affiliation: The Medical Research Council, Mitochondrial Biology Unit, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK.

No MeSH data available.


Crystal packing of HsAPC-1 RD chains, and comparison to previous HsAPC-1 RD structure.A) Seven unique dimer combinations of HsAPC-1 RD in total were superposed upon one another. Each dimer is represented as a cartoon and coloured according to B-factor values as indicated in the key. The two main points of contact between each chain of the dimer are labelled I and II respectively. B) The seven observed chains of the HsAPC-1 RD were superposed on the previously published one (PDB ID: 4N5X). The structures in panel B are coloured by the RMSD difference from 4N5X as in the key. Calcium ions are represented as lime green spheres.
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f0010: Crystal packing of HsAPC-1 RD chains, and comparison to previous HsAPC-1 RD structure.A) Seven unique dimer combinations of HsAPC-1 RD in total were superposed upon one another. Each dimer is represented as a cartoon and coloured according to B-factor values as indicated in the key. The two main points of contact between each chain of the dimer are labelled I and II respectively. B) The seven observed chains of the HsAPC-1 RD were superposed on the previously published one (PDB ID: 4N5X). The structures in panel B are coloured by the RMSD difference from 4N5X as in the key. Calcium ions are represented as lime green spheres.

Mentions: In both crystal space-groups, HsAPC-1 RD was crystallised as a parallel homo-dimer (Fig. 2A). In the previous study, it was crystallised as a monomer, but Cys15 was replaced by serine [16]. The dimer interface is composed of the α-helices of the EF-hands (helices 1, 2, 3, 6, and 7), and is focussed at two contact points, one point from each EF-hand pair. All of the HsAPC-1 RD chains observed here differ slightly from the previous HsAPC-1 RD structure (PDB ID: 4N5X) around α-helices 2 and 3 (Fig. 2B). These α-helices are involved in the first contact point of the dimerisation interface, which could explain these differences.


Calcium-induced conformational changes in the regulatory domain of the human mitochondrial ATP-Mg/Pi carrier.

Harborne SP, Ruprecht JJ, Kunji ER - Biochim. Biophys. Acta (2015)

Crystal packing of HsAPC-1 RD chains, and comparison to previous HsAPC-1 RD structure.A) Seven unique dimer combinations of HsAPC-1 RD in total were superposed upon one another. Each dimer is represented as a cartoon and coloured according to B-factor values as indicated in the key. The two main points of contact between each chain of the dimer are labelled I and II respectively. B) The seven observed chains of the HsAPC-1 RD were superposed on the previously published one (PDB ID: 4N5X). The structures in panel B are coloured by the RMSD difference from 4N5X as in the key. Calcium ions are represented as lime green spheres.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562336&req=5

f0010: Crystal packing of HsAPC-1 RD chains, and comparison to previous HsAPC-1 RD structure.A) Seven unique dimer combinations of HsAPC-1 RD in total were superposed upon one another. Each dimer is represented as a cartoon and coloured according to B-factor values as indicated in the key. The two main points of contact between each chain of the dimer are labelled I and II respectively. B) The seven observed chains of the HsAPC-1 RD were superposed on the previously published one (PDB ID: 4N5X). The structures in panel B are coloured by the RMSD difference from 4N5X as in the key. Calcium ions are represented as lime green spheres.
Mentions: In both crystal space-groups, HsAPC-1 RD was crystallised as a parallel homo-dimer (Fig. 2A). In the previous study, it was crystallised as a monomer, but Cys15 was replaced by serine [16]. The dimer interface is composed of the α-helices of the EF-hands (helices 1, 2, 3, 6, and 7), and is focussed at two contact points, one point from each EF-hand pair. All of the HsAPC-1 RD chains observed here differ slightly from the previous HsAPC-1 RD structure (PDB ID: 4N5X) around α-helices 2 and 3 (Fig. 2B). These α-helices are involved in the first contact point of the dimerisation interface, which could explain these differences.

Bottom Line: Careful analysis by SEC confirmed that although the regulatory domain crystallised as dimers, full-length ATP-Mg/Pi carrier is monomeric.Detailed bioinformatics analyses of different EF-hand states indicate that upon release of calcium, EF-hands close, meaning that the regulatory domain would release the amphipathic α-helix.We propose a mechanism for ATP-Mg/Pi carriers in which the amphipathic α-helix becomes mobile upon release of calcium and could block the transport of substrates across the mitochondrial inner membrane.

View Article: PubMed Central - PubMed

Affiliation: The Medical Research Council, Mitochondrial Biology Unit, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK.

No MeSH data available.