原肌球蛋白结构和功能的多态性。
Polymorphism in tropomyosin structure and function.
机构信息
School of Biosciences, University of Kent, Canterbury, Kent, UK.
出版信息
J Muscle Res Cell Motil. 2013 Aug;34(3-4):177-87. doi: 10.1007/s10974-013-9353-x. Epub 2013 Jul 7.
Abstract
Tropomyosins (Tm) in humans are expressed from four distinct genes and by alternate splicing >40 different Tm polypeptide chains can be made. The functional Tm unit is a dimer of two parallel polypeptide chains and these can be assembled from identical (homodimer) or different (heterodimer) polypeptide chains provided both chains are of the same length. Since most cells express multiple isoforms of Tm, the number of different homo and heterodimers that can be assembled becomes very large. We review the mechanism of dimer assembly and how preferential assembly of some heterodimers is driven by thermodynamic stability. We examine how in vitro studies can reveal functional differences between Tm homo and heterodimers (stability, actin affinity, flexibility) and the implication for how there could be selection of Tm isomers in the assembly on to an actin filament. The role of Tm heterodimers becomes more complex when mutations in Tm are considered, such as those associated with cardiomyopathies, since mutations can appear in only one of the chains.
摘要
人类的原肌球蛋白（Tm）由四个不同的基因表达，通过选择性剪接，可以产生超过 40 种不同的 Tm 多肽链。功能型 Tm 单位是由两条平行多肽链组成的二聚体，只要两条链长度相同，就可以由相同（同源二聚体）或不同（异源二聚体）的多肽链组装而成。由于大多数细胞表达多种 Tm 同工型，因此可以组装的不同同源和异源二聚体的数量变得非常多。我们回顾了二聚体组装的机制，以及某些异源二聚体如何通过热力学稳定性来驱动优先组装。我们研究了体外研究如何揭示 Tm 同源和异源二聚体之间的功能差异（稳定性、肌动蛋白亲和力、灵活性），以及这些差异如何影响 Tm 异构体在肌动蛋白丝上的组装选择。当考虑 Tm 突变时，如与心肌病相关的突变，Tm 异源二聚体的作用变得更加复杂，因为突变可能只出现在其中一条链上。
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