Three-dimensional organization of troponin on cardiac muscle thin filaments in the relaxed state.
Three-dimensional organization of troponin on cardiac muscle thin filaments in the relaxed state.
复制标题
放松状态下心肌细丝上肌钙蛋白的三维组织。
DOI：
10.1016/j.bpj.2014.01.007
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发表时间：
2014
影响因子：
3.4
通讯作者：
Lehman,William
中科院分区：
文献类型：
--
作者：
Yang,Shixin;Barbu-Tudoran,Lucian;Orzechowski,Marek;Craig,Roger;Trinick,John;White,Howard;Lehman,William
肌肉收缩由肌钙蛋白原肌球蛋白调节，肌钙蛋白原肌球蛋白阻断和解锁肌球蛋白在肌动蛋白上的结合部位。为了阐明这种调节机制，必须确定肌钙蛋白和原肌球蛋白在细丝上的三维结构。虽然原肌球蛋白在细丝的电子显微镜螺旋重建中被很好地定义，但肌钙蛋白密度大部分是丢失的。在这里，我们通过对阴性染色的标本应用单颗粒重建程序来测定天然松弛心肌细丝上的肌钙蛋白组织。多个参考模型导致相同的最终结构，表明该过程中没有模型偏差。新的重建清楚地显示了F-肌动蛋白、原肌球蛋白和肌钙蛋白密度。在实现25°分辨率时，肌钙蛋白的定义比以前的重建要好得多。肌钙蛋白密度与肌钙蛋白晶体结构的形状非常相似，便于对电子显微镜密度图的详细解释。肌钙蛋白-T和肌钙蛋白核心区的定位决定了肌钙蛋白的极性。肌钙蛋白-I移动调节域的密度被定位在它可以将原肌球蛋白保持在肌动蛋白的阻断位置，从而暗示了细丝调节的潜在结构基础。我们以前对细丝调节的了解仅限于已知的原肌球蛋白的运动，即立体地阻断和解锁肌球蛋白在肌动蛋白上的结合部位。我们现在展示钙离子感应器肌钙蛋白如何控制这些运动，最终决定肌肉是收缩还是放松。
Muscle contraction is regulated by troponin-tropomyosin, which blocks and unblocks myosin binding sites on actin. To elucidate this regulatory mechanism, the three-dimensional organization of troponin and tropomyosin on the thin filament must be determined. Although tropomyosin is well defined in electron microscopy helical reconstructions of thin filaments, troponin density is mostly lost. Here, we determined troponin organization on native relaxed cardiac muscle thin filaments by applying single particle reconstruction procedures to negatively stained specimens. Multiple reference models led to the same final structure, indicating absence of model bias in the procedure. The new reconstructions clearly showed F-actin, tropomyosin, and troponin densities. At the 25 Å resolution achieved, troponin was considerably better defined than in previous reconstructions. The troponin density closely resembled the shape of troponin crystallographic structures, facilitating detailed interpretation of the electron microscopy density map. The orientation of troponin-T and the troponin core domain established troponin polarity. Density attributable to the troponin-I mobile regulatory domain was positioned where it could hold tropomyosin in its blocking position on actin, thus suggesting the underlying structural basis of thin filament regulation. Our previous understanding of thin filament regulation had been limited to known movements of tropomyosin that sterically block and unblock myosin binding sites on actin. We now show how troponin, the Ca2+sensor, may control these movements, ultimately determining whether muscle contracts or relaxes.
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影响因子：
3
作者：
Paul, D;Patwardhan, A;Morris, EP
通讯作者：
Morris, EP
原肌球蛋白的哪个区域与肌钙蛋白 T 的 N 端一半相互作用？
影响因子：
3.4
作者：
A. Mudalige;S. Lehrer
通讯作者：
S. Lehrer
兔骨骼肌钙蛋白-T 上 α-原肌球蛋白第二个结合区域的鉴定
DOI：
--
发表时间：
1981
期刊：
影响因子：
--
作者：
J. Pearlstone;L. Smillie
通讯作者：
L. Smillie
影响因子：
5.6
作者：
Lehman, W;Hatch, V;Craig, R
通讯作者：
Craig, R
影响因子：
5.6
作者：
Galinska-Rakoczy, Agnieszka;Engel, Patti;Lehman, William
通讯作者：
Lehman, William