Back to Search
Start Over
Investigating the Broad Matrix-Gate Network in the Mitochondrial ADP/ATP Carrier through Molecular Dynamics Simulations.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2022 Feb 05; Vol. 27 (3). Date of Electronic Publication: 2022 Feb 05. - Publication Year :
- 2022
-
Abstract
- The mitochondrial ADP/ATP carrier (AAC) exports ATP and imports ADP through alternating between cytosol-open (c-) and matrix-open (m-) states. The salt bridge networks near the matrix side (m-gate) and cytosol side (c-gate) are thought to be crucial for state transitions, yet our knowledge on these networks is still limited. In the current work, we focus on more conserved m-gate network in the c-state AAC. All-atom molecular dynamics (MD) simulations on a variety of mutants and the CATR-AAC complex have revealed that: (1) without involvement of other positive residues, the charged residues from the three Px[DE]xx[KR] motifs only are prone to form symmetrical inter-helical network; (2) R235 plays a determinant role for the asymmetry in m-gate network of AAC; (3) R235 significantly strengthens the interactions between H3 and H5; (4) R79 exhibits more significant impact on m-gate than R279; (5) CATR promotes symmetry in m-gate mainly through separating R234 from D231 and fixing R79; (6) vulnerability of the H2-H3 interface near matrix side could be functionally important. Our results provide new insights into the highly conserved yet variable m-gate network in the big mitochondrial carrier family.
- Subjects :
- Amino Acid Motifs
Atractyloside chemistry
Atractyloside pharmacology
Binding Sites
Mitochondria metabolism
Mitochondrial ADP, ATP Translocases genetics
Models, Molecular
Molecular Dynamics Simulation
Protein Binding
Protein Conformation
Atractyloside analogs & derivatives
Mitochondrial ADP, ATP Translocases chemistry
Mitochondrial ADP, ATP Translocases metabolism
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 27
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 35164338
- Full Text :
- https://doi.org/10.3390/molecules27031071