Nature communications, 2019-01, Vol.10 (1), p.88-88, Article 88
2019
Details
- Autor(en) / Beteiligte
- Titel
- Inward- and outward-facing X-ray crystal structures of homodimeric P-glycoprotein CmABCB1
- Ist Teil von
- Nature communications, 2019-01, Vol.10 (1), p.88-88, Article 88
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- P-glycoprotein extrudes a large variety of xenobiotics from the cell, thereby protecting tissues from their toxic effects. The machinery underlying unidirectional multidrug pumping remains unknown, largely due to the lack of high-resolution structural information regarding the alternate conformational states of the molecule. Here we report a pair of structures of homodimeric P-glycoprotein: an outward-facing conformational state with bound nucleotide and an inward-facing apo state, at resolutions of 1.9 Å and 3.0 Å, respectively. Features that can be clearly visualized at this high resolution include ATP binding with octahedral coordination of Mg ; an inner chamber that significantly changes in volume with the aid of tight connections among transmembrane helices (TM) 1, 3, and 6; a glutamate-arginine interaction that stabilizes the outward-facing conformation; and extensive interactions between TM1 and TM3, a property that distinguishes multidrug transporters from floppases. These structural elements are proposed to participate in the mechanism of the transporter.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-018-08007-xTitel-ID: cdi_doaj_primary_oai_doaj_org_article_e070bd814c674886ba6ba882b1f3a452
- Format
- –
- Schlagworte
- Adenosine triphosphate, Adenosine Triphosphate - chemistry, Adenosine Triphosphate - metabolism, Arginine, ATP Binding Cassette Transporter, Subfamily B - chemistry, ATP Binding Cassette Transporter, Subfamily B - genetics, ATP Binding Cassette Transporter, Subfamily B - isolation & purification, ATP Binding Cassette Transporter, Subfamily B - metabolism, Conformation, Crystal structure, Crystallography, X-Ray, Enzyme Assays, Glycoproteins, Helices, High resolution, Magnesium, Models, Molecular, Mutagenesis, Site-Directed, P-Glycoprotein, Plant Proteins - chemistry, Plant Proteins - genetics, Plant Proteins - isolation & purification, Plant Proteins - metabolism, Protein Domains - genetics, Protein Multimerization, Protein Structure, Secondary, Recombinant Proteins - chemistry, Recombinant Proteins - genetics, Recombinant Proteins - isolation & purification, Recombinant Proteins - metabolism, Rhodophyta, Structural members, Toxicity, Xenobiotics