3WME

Crystal structure of an inward-facing eukaryotic ABC multidrug transporter

Summary for 3WME

• Entry DOI: 10.2210/pdb3wme/pdb
• Related: 3WMF 3WMG
• Descriptor: ATP-binding cassette, sub-family B, member 1, DECYL-BETA-D-MALTOPYRANOSIDE (3 entities in total)
• Functional Keywords: rec fold, multi drug transporter, transport protein
• Biological source: Cyanidioschyzon merolae
• Total number of polymer chains: 1
• Total formula weight: 66616.24

Authors

Kodan, A.,Yamaguchi, T.,Nakatsu, T.,Kato, H. (deposition date: 2013-11-18, release date: 2014-03-19, Last modification date: 2024-03-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.751 Å)