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| Title | ATP Binding Enables Substrate Release from Multidrug Resistance Protein 1. |
|---|---|
| Journal, issue, pages | Cell, Vol. 172, Issue 1-2, Page 81-89.e10, Year 2018 |
| Publish date | Jan 11, 2018 |
 Authors | Zachary Lee Johnson / Jue Chen /  |
| PubMed Abstract | The multidrug resistance protein MRP1 is an ATP-driven pump that confers resistance to chemotherapy. Previously, we have shown that intracellular substrates are recruited to a bipartite binding site ...The multidrug resistance protein MRP1 is an ATP-driven pump that confers resistance to chemotherapy. Previously, we have shown that intracellular substrates are recruited to a bipartite binding site when the transporter rests in an inward-facing conformation. A key question remains: how are high-affinity substrates transferred across the membrane and released outside the cell? Using electron cryomicroscopy, we show here that ATP binding opens the transport pathway to the extracellular space and reconfigures the substrate-binding site such that it relinquishes its affinity for substrate. Thus, substrate is released prior to ATP hydrolysis. With this result, we now have a complete description of the conformational cycle that enables substrate transfer in a eukaryotic ABC exporter. |
 External links | Cell / PubMed:29290467 |
| Methods | EM (single particle) |
| Resolution | 3.14 Å |
| Structure data | |
| Chemicals |  ChemComp-ATP:  ChemComp-MG:  ChemComp-CLR: |
| Source |
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 Keywords |  TRANSPORT PROTEIN / ABC transporter / multidrug resistance / outward facing |
