2000 Fiscal Year Final Research Report Summary
The recognition and transport mechanism of ions in the proton pump and its intracellular transport
| Project/Area Number |
10470007
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
TAKEGUCHI Noriaki Toyama Medical & Pharmaceutical University Faculty of Pharmaceutical Sciences Prof., 薬学部, 教授 (00019126)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Hideki Toyama Medical & Pharmaceutical University Faculty of Pharmaceutical Sciences Associate Prof., 薬学部, 助教授 (60242509)
ASANO Sinji Toyama Medical & Pharmaceutical University genetic Research Center Associate prof., 遺伝子実験施設, 助教授 (90167891)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Gastric proton pump / Na pump / Gastroenterology / Flippase / Phospholipid |
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| Research Abstract |
The main objects of the present research project are to study the recognition and transport mechanisms of K^+ and H^+ ions in the gastric proton pump and its intracellular transport. The pump consists of α-and β-subunits. First, we explored the binding site of SCH 28080 which is a K^+ competitive inhibitor and found that the previously proposed site by others was wrong and the amino acid residues in transmembrane segment 6 of the α subunit of the pump are involved in SCH 28080 binding. From our chimera study between proton pump and Na pump, we found that the amino acid residues in transmembrane segment 6 are involved in K^+ and H^+ recognition. Glu in the transmembrane segment 4 is involved in K^+ binding and the K^+ -dependent conformational change of the α subunit. we also explored the role of the βsubunit of the pump. We found that the four consecutive amino acid sequence located just outside the extracellular part of the membrane has the proton pump destination signal in the cell. Carbohydrate chains in this subunit also has the destination signal and involved in the enzyme activity of the pump. The extracellular S-S cross links in the β-subunit had the important role in the enzyme reaction. The apical cell surface of the gastric parietal cell must, have a protective mechanism against the strong acid secreted by the cell itself. As a possible machinery for this end, we found the presence of a flippase, which can secrete both phosphatidylcholine and phosphatidylserine. The secreted phospholipids may serve as a hydrophopbic lining and rejects acid.
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