Harborne, Steven P D, King, Martin S, Crichton, Paul G ORCID: https://orcid.org/0000-0003-3786-8359 and Kunji, Edmund R S
(2017)
Calcium regulation of the human mitochondrial ATP-Mg/Pi carrier SLC25A24 uses a locking pin mechanism.
Scientific Reports, 7.
ISSN 2045-2322
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Abstract
Mitochondrial ATP-Mg/Pi carriers import adenine nucleotides into the mitochondrial matrix and export phosphate to the cytosol. They are calcium-regulated to control the size of the matrix adenine nucleotide pool in response to cellular energetic demands. They consist of three domains: an N-terminal regulatory domain containing four calcium-binding EF-hands, a linker loop domain with an amphipathic α-helix and a C-terminal mitochondrial carrier domain for the transport of substrates. Here, we use thermostability assays to demonstrate that the carrier is regulated by calcium via a locking pin mechanism involving the amphipathic α-helix. When calcium levels in the intermembrane space are high, the N-terminus of the amphipathic α-helix is bound to a cleft in the regulatory domain, leading to substrate transport by the carrier domain. When calcium levels drop, the cleft closes, and the amphipathic α-helix is released to bind to the carrier domain via its C-terminus, locking the carrier in an inhibited state.
Item Type: | Article |
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Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
Depositing User: | Pure Connector |
Date Deposited: | 04 Apr 2017 05:29 |
Last Modified: | 19 Oct 2023 01:57 |
URI: | https://ueaeprints.uea.ac.uk/id/eprint/63157 |
DOI: | 10.1038/srep45383 |
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