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| Content Provider | Springer Nature Link |
|---|---|
| Author | Lü, Shouqin An, Hailong Zhang, Hailin Long, Mian |
| Copyright Year | 2015 |
| Abstract | The effect of the conserved Leu/Ile site in the CD loop on the gating dynamics of Kir channels and corresponding micro-structural mechanism remains unclear. Molecular dynamics simulations were performed to investigate the structural mechanism of chicken Kir2.2. Compared to WT, the I223L mutant channel bound to PIP$_{2}$ more strongly, was activated more rapidly, and maintained the activation state more stably after PIP$_{2}$ dissociation. Cellular electrophysiology assays of mouse Kir2.1 and human Kir2.2 indicated that, consistent with simulations, the Leu residue increased the channel responses to PIP$_{2}$ through increased binding affinity and faster activation kinetics, and the deactivation kinetics decreased upon PIP$_{2}$ inhibition. The Ile residue induced the opposite responses. This difference was attributed to the distinct hydrophobic side chain symmetries of Leu and Ile; switching between these residues caused the interaction network to redistribute and offered effective conformation transduction in the Leu systems, which had more rigid and independent subunits. |
| Starting Page | 5948 |
| Ending Page | 5961 |
| Page Count | 14 |
| File Format | |
| ISSN | 08937648 |
| Journal | Molecular Neurobiology |
| Volume Number | 53 |
| Issue Number | 9 |
| e-ISSN | 15591182 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2015-10-31 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Inward-rectifier potassium channel Molecular dynamics simulations Conformational change Patch clamp Structure-function relationship Neurosciences Neurobiology Cell Biology Neurology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Cellular and Molecular Neuroscience |
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