7VLR

Structure of SUR2B in complex with Mg-ATP/ADP

Summary for 7VLR

• Entry DOI: 10.2210/pdb7vlr/pdb
• EMDB information: 32024
• Descriptor: Isoform SUR2B of ATP-binding cassette sub-family C member 9, CHOLESTEROL HEMISUCCINATE, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: sur2b, abc transporter, membrane protein
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 1
• Total formula weight: 175958.28

Authors

Chen, L.,Ding, D. (deposition date: 2021-10-05, release date: 2022-05-18, Last modification date: 2024-06-19)

Primary citation

Ding, D.,Wu, J.X.,Duan, X.,Ma, S.,Lai, L.,Chen, L.
Structural identification of vasodilator binding sites on the SUR2 subunit.
Nat Commun, 13:2675-2675, 2022

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 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.

PubMed: 35562524
DOI: 10.1038/s41467-022-30428-y

Experimental method

ELECTRON MICROSCOPY (3.4 Å)