8SWN
Bovine multidrug resistance protein 4 (MRP4) E1202Q mutant bound to ATP in MSP lipid nanodisc
Summary for 8SWN
| Entry DOI | 10.2210/pdb8swn/pdb |
| EMDB information | 40821 |
| Descriptor | ATP binding cassette subfamily C member 4, MAGNESIUM ION, PHOSPHATIDYLETHANOLAMINE, ... (4 entities in total) |
| Functional Keywords | abc transporter, multidrug resistance-associated protein, membrane protein, transport protein |
| Biological source | Bos taurus (cattle) |
| Total number of polymer chains | 1 |
| Total formula weight | 151383.32 |
| Authors | Pourmal, S.,Stroud, R.M. (deposition date: 2023-05-19, release date: 2024-01-17, Last modification date: 2024-05-01) |
| Primary citation | Pourmal, S.,Green, E.,Bajaj, R.,Chemmama, I.E.,Knudsen, G.M.,Gupta, M.,Sali, A.,Cheng, Y.,Craik, C.S.,Kroetz, D.L.,Stroud, R.M. Structural basis of prostaglandin efflux by MRP4. Nat.Struct.Mol.Biol., 31:621-632, 2024 Cited by PubMed Abstract: Multidrug resistance protein 4 (MRP4) is a broadly expressed ATP-binding cassette transporter that is unique among the MRP subfamily for transporting prostanoids, a group of signaling molecules derived from unsaturated fatty acids. To better understand the basis of the substrate selectivity of MRP4, we used cryogenic-electron microscopy to determine six structures of nanodisc-reconstituted MRP4 at various stages throughout its transport cycle. Substrate-bound structures of MRP4 in complex with PGE, PGE and the sulfonated-sterol DHEA-S reveal a common binding site that accommodates a diverse set of organic anions and suggest an allosteric mechanism for substrate-induced enhancement of MRP4 ATPase activity. Our structure of a catalytically compromised MRP4 mutant bound to ATP-Mg is outward-occluded, a conformation previously unobserved in the MRP subfamily and consistent with an alternating-access transport mechanism. Our study provides insights into the endogenous function of this versatile efflux transporter and establishes a basis for MRP4-targeted drug design. PubMed: 38216659DOI: 10.1038/s41594-023-01176-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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