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| Title | Structural identification of vasodilator binding sites on the SUR2 subunit. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 2675, Year 2022 |
| Publish date | May 13, 2022 |
 Authors | Dian Ding / Jing-Xiang Wu / Xinli Duan / Songling Ma / Lipeng Lai / Lei Chen /  |
| PubMed Abstract | ATP-sensitive potassium channels (K), composed of Kir6 and SUR subunits, convert the metabolic status of the cell into electrical signals. Pharmacological activation of SUR2- containing K channels by ...ATP-sensitive potassium channels (K), composed of Kir6 and SUR subunits, convert the metabolic status of the cell into electrical signals. Pharmacological activation of SUR2- containing K channels by class of small molecule drugs known as K openers leads to hyperpolarization of excitable cells and to vasodilation. Thus, K openers could be used to treat cardiovascular diseases. However, where these vasodilators bind to K and how they activate the channel remains elusive. Here, we present cryo-EM structures of SUR2A and SUR2B subunits in complex with Mg-nucleotides and P1075 or levcromakalim, two chemically distinct K openers that are specific to SUR2. Both P1075 and levcromakalim bind to a common site in the transmembrane domain (TMD) of the SUR2 subunit, which is between TMD1 and TMD2 and is embraced by TM10, TM11, TM12, TM14, and TM17. These K openers synergize with Mg-nucleotides to stabilize SUR2 in the NBD-dimerized occluded state to activate the channel. |
 External links | Nat Commun / PubMed:35562524 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.1 - 3.4 Å |
| Structure data | EMDB-32024, PDB-7vlr: EMDB-32025, PDB-7vls: EMDB-32026, PDB-7vlt: EMDB-32027, PDB-7vlu: |
| Chemicals |  ChemComp-Y01:  ChemComp-ADP:  ChemComp-MG:  ChemComp-ATP:  ChemComp-ESV:  ChemComp-ETJ: |
| Source |
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 Keywords |  MEMBRANE PROTEIN / SUR2B / ABC transporter / P1075 / levcromakalim / SUR2A |
