8KCI
ATP-bound hMRP5 outward-open
Summary for 8KCI
| Entry DOI | 10.2210/pdb8kci/pdb |
| EMDB information | 37105 |
| Descriptor | ATP-binding cassette sub-family C member 5, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION (3 entities in total) |
| Functional Keywords | atp-bound hmrp5 outward-open, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 161878.78 |
| Authors | |
| Primary citation | Huang, Y.,Xue, C.,Bu, R.,Wu, C.,Li, J.,Zhang, J.,Chen, J.,Shi, Z.,Chen, Y.,Wang, Y.,Liu, Z. Inhibition and transport mechanisms of the ABC transporter hMRP5. Nat Commun, 15:4811-4811, 2024 Cited by PubMed Abstract: Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters. PubMed: 38844452DOI: 10.1038/s41467-024-49204-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.94 Å) |
Structure validation
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