Isomorphisms in tropomyosin modulate binding, flexibility and thin filament function

生物体会移动。最壮观的例子是显微镜下条纹状的肌肉。我们每天的血液循环、姿势、速度都依赖于它们，不同类型的肌肉——快肌、慢肌和心肌——利用肌丝蛋白的异构体来收缩和放松。蛋白质同工异构体就像表亲；它们具有家族相似性，但有不同的特征（如氨基酸序列略有不同）。原肌球蛋白如何促进肌肉多样性一直是一个谜。原肌球蛋白的主要亚型是Tpm1.1。它们共有39个氨基酸取代。大问题：他们的做法有什么不同？直到最近才有答案（Lohmeier-Vogel 50），还没有在蛋白质水平上进行研究。(2)部分。在极端条件下的原肌球蛋白对蛋白质来说，寒冷的问题是它的刚性。在冬季，北大西洋接近冰点，与温血动物（哺乳动物）的情况相比，下降了30摄氏度。然而这是一个自然的海洋栖息地。一个“大”问题是：原肌球蛋白是如何避免被“束缚”的？最近的工作（Fudge & Heeley 2015）表明，鲑鱼Tpm1.1中存在3种“弯曲”策略（更少的离子对，更多的甘氨酸和核心位点的极性残基）。这些“冷同构”对鲑鱼Tpm1.1功能的影响——聚合、肌钙蛋白结合和调节——将通过与热稳定的哺乳动物同源氨基酸交换来探测。第(2)部分和第(1)部分一样，将提供原肌凝蛋白功能图谱（即结合位点）的信息。

Living organisms move. The most spectacular examples are muscles that have a striped appearance under the microscope. We rely on them daily for blood circulation, posture, speed is an outcome of different types of muscle - fast, slow and cardiac - that deploy isoforms of the myofilament proteins to contract and relax. Protein isoforms are like cousins; they bear a family resemblance but have distinguishing features (eg slightly different amino acid sequences). How tropomyosin contributes to muscle diversity has long-been an enigma. The major isoforms of tropomyosin are Tpm1.1 (formerly ) ). They share 39 amino acid substitutions. The 'big' Q. What do they do differently? was answered only recently (Lohmeier-Vogel 50) not yet studied at the protein level.Part (II). Tropomyosin in extreme conditions The problem of cold for a protein is rigidity. During the winter, the N. Atlantic approaches freezing, a drop of > 30 oC compared to the warm-blooded (mammalian) scenario. Yet this is a natural marine habitat. A 'big' Q. is: How does tropomyosin avoid being straitjacketed'? Recent work (Fudge & Heeley 2015) has shown the existence of 3 'flexing' strategies (fewer ion pairs, more glycine & polar residues in core sites) within salmon Tpm1.1. The effect of these 'cold isomorphisms' on salmon Tpm1.1 function - polymerisation, troponin binding & regulation - will be probed by interchange of amino acids with the thermally-stable mammalian homologue. Part (II), as with Part (I), will provide information on tropomyosin's functional landscape (ie binding sites).