Isomorphisms in tropomyosin modulate binding, flexibility and thin filament function

原肌球蛋白的同构调节结合、柔韧性和细丝功能

• 批准号: RGPIN-2017-06010
• 负责人: Heeley, David
• 金额: $ 1.89万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744079
• 关键词: Isomorphisms; tropomyosin; modulate; binding; flexibility

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).

生物体移动。最壮观的例子是肌肉在显微镜下有条纹外观。我们每天依靠它们进行血液循环，姿势，速度是不同类型肌肉的结果-快，慢和心脏-部署肌丝蛋白的亚型来收缩和放松。蛋白质异构体就像表兄弟;它们具有家族相似性，但具有区别性特征（例如略有不同的氨基酸序列）。原肌球蛋白如何促进肌肉多样性一直是个谜。原肌球蛋白的主要同种型是Tpm 1.1（以前））。 它们共有39个氨基酸替换。“大”Q他们有什么不同的做法？ 回答最近（Lohmeier-Vogel 50）尚未研究在蛋白质水平。极端条件下的原肌球蛋白寒冷对蛋白质来说的问题是刚性。在冬季，N.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摄氏度以上。然而，这是一个天然的海洋栖息地。一个大Q。原肌球蛋白如何避免被束缚？最近的工作（Fudge & Heeley 2015）已经表明在鲑鱼Tpm 1.1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中的极性残基）。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物交换氨基酸来探测。第二部分，与第一部分一样，将提供原肌球蛋白的功能景观（即结合位点）的信息。