2014年3月
Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- 巻
- 111
- 号
- 11
- 開始ページ
- 4049
- 終了ページ
- 4054
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1073/pnas.1321562111
- 出版者・発行元
- NATL ACAD SCIENCES
P-glycoprotein is an ATP-binding cassette multidrug transporter that actively transports chemically diverse substrates across the lipid bilayer. The precise molecular mechanism underlying transport is not fully understood. Here, we present crystal structures of a eukaryotic P-glycoprotein homolog, CmABCB1 from Cyanidioschyzon merolae, in two forms: unbound at 2.6-angstrom resolution and bound to a unique allosteric inhibitor at 2.4-angstrom resolution. The inhibitor clamps the transmembrane helices from the outside, fixing the CmABCB1 structure in an inward-open conformation similar to the unbound structure, confirming that an outward-opening motion is required for ATP hydrolysis cycle. These structures, along with site-directed mutagenesis and transporter activity measurements, reveal the detailed architecture of the transporter, including a gate that opens to extracellular side and two gates that open to intramembranous region and the cytosolic side. We propose that the motion of the nucleotide-binding domain drives those gating apparatuses via two short intracellular helices, IH1 and IH2, and two transmembrane helices, TM2 and TM5.
- リンク情報
-
- DOI
- https://doi.org/10.1073/pnas.1321562111
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/24591620
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000333027900045&DestApp=WOS_CPL
- 共同研究・競争的資金等の研究課題
- ABC輸送体の分子機構の解明
- 共同研究・競争的資金等の研究課題
- ABC輸送体のX線結晶構造解析
- ID情報
-
- DOI : 10.1073/pnas.1321562111
- ISSN : 0027-8424
- PubMed ID : 24591620
- Web of Science ID : WOS:000333027900045