Elucidation of the molecular mechanism of ABC transporters

2014 Fiscal Year Final Research Report

• Project/Area Number: 24689029
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Kyoto University
• Principal Investigator: KODAN Atsushi 京都大学, 物質ー細胞統合システム拠点, 助教 (80360543)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 生体分子 / 膜タンパク質 / 癌 / 多剤耐性 / 立体構造解析 / X線結晶構造解析 / ABCタンパク質 / P糖タンパク質

Outline of Final Research Achievements

In this study, the highest-resolution crystal structures of a eukaryotic P-glycoprotein homolog from the red algae Cyanidioschyzon merolae, were determined in two forms: unbound at 2.6-angstrom resolution and bound to a unique allosteric inhibitor at 2.4-angstrom resolution. 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.

Free Research Field

構造生物学、生化学