Calcium regulation of the human mitochondrial ATP-Mg/Pi carrier SLC25A24 uses a locking pin mechanism.
Sci Rep
; 7: 45383, 2017 03 28.
Article
em En
| MEDLINE
| ID: mdl-28350015
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
/
Cálcio
/
Antiporters
/
Proteínas Mitocondriais
/
Subunidade Apc1 do Ciclossomo-Complexo Promotor de Anáfase
/
Mitocôndrias
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article