Tropomyosin and troponin cooperativity on the thin filament.
Tropomyosin and troponin cooperativity on the thin filament.
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DOI：
10.1007/978-4-431-38453-3_10
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发表时间：
2007
影响因子：
--
通讯作者：
S. Boussouf;M. Geeves
中科院分区：
文献类型：
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作者：
S. Boussouf;M. Geeves
自40年前首次发现这些蛋白质以来，细丝蛋白原肌球蛋白（Tm）和肌钙蛋白（Tn）对肌肉收缩的调节一直是一个令人感兴趣的领域。1，2尽管我们对这些蛋白质本身及其调节肌肉收缩的机制有了大量了解，但该机制的某些方面仍有待充分解释。我们感兴趣的是钙调节过程的协同性，这仍然知之甚少，已经提出了几种不同的模型。最简单的话，问题的本质可以简单地概括出来.在骨骼肌中，钙与TnC的两个调节位点的结合是激活肌肉收缩所必需的。分离的TnC与钙协同结合，如对于两个钙离子开关所预期的那样，希尔系数（h）在1和2.3，4之间。相反，在带皮肌纤维中等长力的钙激活发生在更大的希尔系数5，6，导致协同性延伸超出细丝的单个肌动蛋白7TmTn结构单元的想法。一些模型的肌肉激活建议整个丝开关作为一个单一的单位，而在溶液中的纯化蛋白质的研究往往表明更有限的cooperativity延伸到最近的邻居actin7TmTn单位。在本文中，为什么性质的协同性仍然是一个问题的原因将探讨一起概述我们最近的研究在溶液中的蛋白质揭示了细丝协同性。
The regulation of muscle contraction by the thin filament proteins tropomyosin (Tm) and troponin (Tn) has remained an area of interest since the proteins were first discovered 40 years ago.1,2 Although we have learnt a great deal about the proteins themselves and the mechanism by which they regulate muscle contraction some aspects of the mechanism remain to be adequately explained. Our interest is in the cooperativity of the calcium regulatory process and this remains poorly understood and several different models have been proposed. At it simplest the essence of the problem can be simply outlined. In skeletal muscle the binding of calcium to the two regulatory sites of TnC is required for activation of muscle contraction. Isolated TnC binds the calcium cooperatively, as might be expected for a two-calcium-ion switch, with a hill coefficient (h) of between 1 & 2.3,4 In contrast the calcium activation of isometric force in a skinned muscle fibre occurs with a much larger hill coefficient5,6 leading to the idea that cooperativity extends beyond the single actin7TmTn structural unit of the thin filament. Some models of muscle activation suggest the whole filament switches as a single unit while studies of the purified proteins in solution tend to indicate more limited cooperativity extending to only the nearest neighbour actin7TmTn units. In this paper the reasons why the nature of the cooperativity remains a problem will be explored together with an overview of what our recent studies of the proteins in solution have revealed about thin filament cooperativity.