論文

2019年12月1日

Inward- and outward-facing X-ray crystal structures of homodimeric P-glycoprotein CmABCB1

Nature Communications
  • Atsushi Kodan
  • ,
  • Tomohiro Yamaguchi
  • ,
  • Toru Nakatsu
  • ,
  • Keita Matsuoka
  • ,
  • Yasuhisa Kimura
  • ,
  • Kazumitsu Ueda
  • ,
  • Hiroaki Kato

10
DOI
10.1038/s41467-018-08007-x

© 2019, The Author(s). 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 2+ ; 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.

リンク情報
DOI
https://doi.org/10.1038/s41467-018-08007-x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30622258
URL
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85059741345&origin=inward

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