3WMG

Crystal structure of an inward-facing eukaryotic ABC multidrug transporter G277V/A278V/A279V mutant in complex with an cyclic peptide inhibitor, aCAP

3WMG の概要

• エントリーDOI: 10.2210/pdb3wmg/pdb
• 関連するPDBエントリー: 3WME 3WMF
• 関連するBIRD辞書のPRD_ID: PRD_001229
• 分子名称: ATP-binding cassette, sub-family B, member 1, anti-CmABCB1 peptide, DECYL-BETA-D-MALTOPYRANOSIDE, ... (5 entities in total)
• 機能のキーワード: rec fold, multi drug transporter, macrocyclic peptide, transport protein-inhibitor complex, transport protein/inhibitor
• 由来する生物種: Cyanidioschyzon merolae; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72066.43

構造登録者

Kodan, A.,Yamaguchi, T.,Nakatsu, T.,Sakiyama, K.,Hipolito, C.J.,Fujioka, A.,Hirokane, R.,Ikeguchi, K.,Watanabe, B.,Hirtake, J.,Kimura, Y.,Suga, H.,Ueda, K.,Kato, H. (登録日: 2013-11-18, 公開日: 2014-04-30, 最終更新日: 2024-10-30)

主引用文献

Kodan, A.,Yamaguchi, T.,Nakatsu, T.,Sakiyama, K.,Hipolito, C.J.,Fujioka, A.,Hirokane, R.,Ikeguchi, K.,Watanabe, B.,Hiratake, J.,Kimura, Y.,Suga, H.,Ueda, K.,Kato, H.
Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog.
Proc.Natl.Acad.Sci.USA, 111:4049-4054, 2014

PubMed Abstract: 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-Å resolution and bound to a unique allosteric inhibitor at 2.4-Å 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.

PubMed: 24591620
DOI: 10.1073/pnas.1321562111

実験手法

X-RAY DIFFRACTION (2.4 Å)