7Y1K
Structure of SUR2A in complex with Mg-ATP, Mg-ADP and repaglinide in the inward-facing conformation
Summary for 7Y1K
| Entry DOI | 10.2210/pdb7y1k/pdb |
| EMDB information | 33564 |
| Descriptor | ATP-binding cassette sub-family C member 9, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total) |
| Functional Keywords | sur2a, abc transporter, repaglinide, membrane protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 1 |
| Total formula weight | 175736.00 |
| Authors | |
| Primary citation | Ding, D.,Hou, T.,Wei, M.,Wu, J.X.,Chen, L. The inhibition mechanism of the SUR2A-containing K ATP channel by a regulatory helix. Nat Commun, 14:3608-3608, 2023 Cited by PubMed Abstract: K channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing K channels differ from other subtypes in their sensitivity to Mg-ADP activation. However, the underlying structural mechanism remains poorly understood. Here we present a series of cryo-EM structures of SUR2A in the presence of different combinations of Mg-nucleotides and the allosteric inhibitor repaglinide. These structures uncover regulatory helix (R helix) on the NBD1-TMD2 linker, which wedges between NBD1 and NBD2. R helix stabilizes SUR2A in the NBD-separated conformation to inhibit channel activation. The competitive binding of Mg-ADP with Mg-ATP to NBD2 mobilizes the R helix to relieve such inhibition, allowing channel activation. The structures of SUR2B in similar conditions suggest that the C-terminal 42 residues of SUR2B enhance the structural dynamics of NBD2 and facilitate the dissociation of the R helix and the binding of Mg-ADP to NBD2, promoting NBD dimerization and subsequent channel activation. PubMed: 37330603DOI: 10.1038/s41467-023-39379-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
Download full validation report
