2005 Fiscal Year Final Research Report Summary
Mechanism in Energy Transduction of Ca^<2+> Pump and Molecular Basis of Related Genetic Diseases
| Project/Area Number |
16370066
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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 |
Biophysics
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
SUZUKI Hiroshi Asahikawa Medical College, School of Medicine, Professor, 医学部, 教授 (50183421)
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| Co-Investigator(Kenkyū-buntansha) |
DAIHO Takashi Asahikawa Medical College, School of Medicine, Assistant Professor, 医学部, 助教授 (90207267)
YAMASAKI Kazuo Asahikawa Medical College, School of Medicine, Research Associate, 医学部, 助手 (60241428)
KATO Sanae Asahikawa Medical College, School of Medicine, Research Associate, 医学部, 助手 (80291061)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Ca^<2+> pump / Ca^<2+>-ATPase / Sarco(endo)plasmic reticulum / Darier disease / Hailey-Hailey disease / Golgi apparatus / Ca^<2+> / Mn^<2+> pump / Ca^<2+> / Mn^<2+>-ATPase |
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| Research Abstract |
Sarco(endo)plasmic reticulum Ca^<2+>-ATPases is the representative members of P-type ATPase family and catalyze Ca^<2+> transport coupled with ATP hydrolysis. The Ca^<2+>-ATPase consists of the three cytoplasmic domains (Nucleotide binding (N), Phosphorylation (P), and Actuator (A)) and ten transmembrane helices (M1〜M10, or eleven M11 in the SERCA2b isoform). The Ca^<2+>-ATPase forms an auto-phosphorylated intermediate (EP) during the transport cycle.
In this research, we revealed and found the followings :
1)The large motions of the cytoplasmic three domains and the changes in their interactions take place during the Ca^<2+> transport cycle.
2)The large rotation of the A domain and its tight association with the P domain take place for the isomerization of EP (i.e.E1P to E2P isomerization).
3)The strong interactions at the two specific regions of the A-P domain interface in E2P are critical for the Ca^<2+> release into the lumen and also critical for the E2P hydrolysis after the Ca^<2+> release. We could identify the structural elements involved in these domain-motions and -interactions and reveal their actual roles in the Ca^<2+>-transport.
4)We developed successfully the stable structural analogs of the phosphorylated intermediates and revealed their characteristic properties, hence contributed to their atomic level structural studies.
5)We revealed the molecular defects of SERCA2b associated with the Darier-disease causing 51 mutations in the 51 pedigrees (most of the substitutions and deletions of residues reported so far).
6)We found the specific expression and localization of the Golgi Ca^<2+>/Mn^<2+>-ATPase, another member of the P-type ATPase family, of which genetic defects causes Hailey-Hailey disease. We also predicted its function in the cell differentiation.
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Research Products
(28 results)
