| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
ABC transporters transport substrates in association with conformational change between the inward- and outward-facing states. We have determined these two state structures of an ABC multidrug transporter P-glycoprotein homolog, CmABCB1, at high resolution, and thus became to elucidate the relationship between conformational change and substrate transport. In this study, a crystal structure at an intermediate state of CmABCB1 mutant was determined. By comparison with the inward- and outward-structures of CmABCB1, this intermediate structure suggested that the interaction with a substrate was altered in conformational change. The mutation of the amino acid residues contributing the change the substrate interaction disrupted the transport activity. These results suggest that P-glycoprotein transports substrates by weakening the interaction of substrates by contracting the inner cavity involving substrate binding sites.
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