8AYQ
NaK C-DI mutant with Rb+ and Ca2+
Summary for 8AYQ
| Entry DOI | 10.2210/pdb8ayq/pdb |
| Related | 8AYP |
| Descriptor | Potassium channel protein, RUBIDIUM ION, CALCIUM ION, ... (6 entities in total) |
| Functional Keywords | ion channel, prokaryote, membrane protein, transport protein |
| Biological source | Bacillus cereus ATCC 14579 |
| Total number of polymer chains | 4 |
| Total formula weight | 45643.05 |
| Authors | Minniberger, S.,Plested, A.J.R. (deposition date: 2022-09-02, release date: 2023-02-22, Last modification date: 2024-02-07) |
| Primary citation | Schackert, F.K.,Biedermann, J.,Abdolvand, S.,Minniberger, S.,Song, C.,Plested, A.J.R.,Carloni, P.,Sun, H. Mechanism of Calcium Permeation in a Glutamate Receptor Ion Channel. J.Chem.Inf.Model., 63:1293-1300, 2023 Cited by PubMed Abstract: The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are neurotransmitter-activated cation channels ubiquitously expressed in vertebrate brains. The regulation of calcium flux through the channel pore by RNA-editing is linked to synaptic plasticity while excessive calcium influx poses a risk for neurodegeneration. Unfortunately, the molecular mechanisms underlying this key process are mostly unknown. Here, we investigated calcium conduction in calcium-permeable AMPAR using Molecular Dynamics (MD) simulations with recently introduced multisite force-field parameters for Ca. Our calculations are consistent with experiment and explain the distinct calcium permeability in different RNA-edited forms of GluA2. For one of the identified metal binding sites, multiscale Quantum Mechanics/Molecular Mechanics (QM/MM) simulations further validated the results from MD and revealed small but reproducible charge transfer between the metal ion and its first solvation shell. In addition, the ion occupancy derived from MD simulations independently reproduced the Ca binding profile in an X-ray structure of an NaK channel mimicking the AMPAR selectivity filter. This integrated study comprising X-ray crystallography, multisite MD, and multiscale QM/MM simulations provides unprecedented insights into Ca permeation mechanisms in AMPARs, and paves the way for studying other biological processes in which Ca plays a pivotal role. PubMed: 36758214DOI: 10.1021/acs.jcim.2c01494 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.75 Å) |
Structure validation
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