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| Title | Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome. |
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| Journal, issue, pages | Cell, Vol. 169, Issue 6, Page 1042-11050.e9, Year 2017 |
| Publish date | Jun 1, 2017 |
 Authors | Ji Sun / Roderick MacKinnon /  |
| PubMed Abstract | KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present ...KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP-free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP. CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP, and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. |
 External links | Cell / PubMed:28575668 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.7 Å |
| Structure data | |
| Chemicals |  ChemComp-CA: |
| Source |
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 Keywords | TRANSPORT PROTEIN / CALCIUM BINDING PROTEIN / KCNQ1-CaM complex / potassium channel / Long QT syndrome |
xenopus laevis (African clawed frog)
homo sapiens (human)
