| Project/Area Number |
23612005
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Mechanobiology
|
|---|
| Research Institution | Jikei University School of Medicine |
|---|
Principal Investigator |
YAMAGUCHI Maki 東京慈恵会医科大学, 医学部, 講師 (30271315)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKEMORI Shigeru 東京慈恵会医科大学, 医学部, 教授 (20179675)
OHNO Tetsuo 東京慈恵会医科大学, 医学部, 助教 (30233224)
KIMURA Masako 女子栄養大学, 栄養学部, 准教授 (30328314)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
AKIYAMA Nobutake 東京慈恵会医科大学, 医学部, 講師 (00338865)
|
|---|
| Project Period (FY) |
2011 – 2013
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | 心筋症 / X線回折 / 分子動力学 / トロポニン / Ｘ線回折 |
|---|
| Research Abstract |
The E244D- and K247R-troponin-T (TnT) mutants, which cause familial hypertrophic cardiomyopathy, have been shown to enhance calcium-dependent contraction on cardiac muscle. To clarify the mechanism of this enhancement, we performed molecular dynamics simulation of troponin molecule as well as X-ray diffraction experiments with cardiac muscle fibers to which wild-type/E244D/K247R mutant TnT had been introduced in the absence of troponin I (TnI). When E244D-TnT was introduced into the cardiac fibers, intensity ratio of the equatorial reflection (1,1/1,0), which reflects amount of the interacting myosin to actin increased compared with those to which wild-type-TnT were introduced. On the other hand, molecular dynamics simulation revealed that interaction betweeen TnT and TnI were changed in K247R-TnT mutants. These results indicate that in these two mutants, enhanced tension development would be induced by totally different mechanisms to trigger the hypertrophy of cardiac muscle.
|
