7OTG
Structure of ABCB1/P-glycoprotein in the presence of the CFTR potentiator ivacaftor
Summary for 7OTG
| Entry DOI | 10.2210/pdb7otg/pdb |
| EMDB information | 13059 |
| Descriptor | Multidrug resistance protein 1A, N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (2 entities in total) |
| Functional Keywords | abcb1, abc transporters, membrane proteins, ivacaftor, mdr1, multidrug resistance, cryo-em, membrane protein |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 142270.37 |
| Authors | Ford, R.C.,Barbieri, A.,Thonghin, N.,Shafi, T.,Prince, S.M.,Collins, R.F. (deposition date: 2021-06-10, release date: 2021-12-08, Last modification date: 2024-07-17) |
| Primary citation | Barbieri, A.,Thonghin, N.,Shafi, T.,Prince, S.M.,Collins, R.F.,Ford, R.C. Structure of ABCB1/P-Glycoprotein in the Presence of the CFTR Potentiator Ivacaftor. Membranes (Basel), 11:-, 2021 Cited by PubMed Abstract: ABCB1/P-glycoprotein is an ATP binding cassette transporter that is involved in the clearance of xenobiotics, and it affects the disposition of many drugs in the body. Conformational flexibility of the protein within the membrane is an intrinsic part of its mechanism of action, but this has made structural studies challenging. Here, we have studied different conformations of P-glycoprotein simultaneously in the presence of ivacaftor, a known competitive inhibitor. In order to conduct this, we used high contrast cryo-electron microscopy imaging with a Volta phase plate. We associate the presence of ivacaftor with the appearance of an additional density in one of the conformational states detected. The additional density is in the central aqueous cavity and is associated with a wider separation of the two halves of the transporter in the inward-facing state. Conformational changes to the nucleotide-binding domains are also observed and may help to explain the stimulation of ATPase activity that occurs when transported substrate is bound in many ATP binding cassette transporters. PubMed: 34940424DOI: 10.3390/membranes11120923 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (5.4 Å) |
Structure validation
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