Structural highlights
Publication Abstract from PubMed
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.
ATP Binding Enables Substrate Release from Multidrug Resistance Protein 1.,Johnson ZL, Chen J Cell. 2018 Jan 11;172(1-2):81-89.e10. doi: 10.1016/j.cell.2017.12.005. Epub 2017 , Dec 28. PMID:29290467[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Johnson ZL, Chen J. ATP Binding Enables Substrate Release from Multidrug Resistance Protein 1. Cell. 2018 Jan 11;172(1-2):81-89.e10. doi: 10.1016/j.cell.2017.12.005. Epub 2017 , Dec 28. PMID:29290467 doi:http://dx.doi.org/10.1016/j.cell.2017.12.005
