Matityahu Avi, Onn Itay
Faculty of Medicine in the Galilee, Bar-Ilan University, 8 Henrietta Szold St., P.O. Box 1589, 1311502, Safed, Israel.
Curr Genet. 2018 Feb;64(1):109-116. doi: 10.1007/s00294-017-0735-2. Epub 2017 Aug 23.
The higher-order organization of chromosomes ensures their stability and functionality. However, the molecular mechanism by which higher order structure is established is poorly understood. Dissecting the activity of the relevant proteins provides information essential for achieving a comprehensive understanding of chromosome structure. Proteins of the structural maintenance of chromosome (SMC) family of ATPases are the core of evolutionary conserved complexes. SMC complexes are involved in regulating genome dynamics and in maintaining genome stability. The structure of all SMC proteins resembles an elongated rod that contains a central coiled-coil domain, a common protein structural motif in which two α-helices twist together. In recent years, the imperative role of the coiled-coil domain to SMC protein activity and regulation has become evident. Here, we discuss recent advances in the function of the SMC coiled coils. We describe the structure of the coiled-coil domain of SMC proteins, modifications and interactions that are mediated by it. Furthermore, we assess the role of the coiled-coil domain in conformational switches of SMC proteins, and in determining the architecture of the SMC dimer. Finally, we review the interplay between mutations in the coiled-coil domain and human disorders. We suggest that distinctive properties of coiled coils of different SMC proteins contribute to their distinct functions. The discussion clarifies the mechanisms underlying the activity of SMC proteins, and advocates future studies to elucidate the function of the SMC coiled coil domain.
染色体的高级组织确保了它们的稳定性和功能性。然而，高阶结构形成的分子机制却知之甚少。剖析相关蛋白质的活性为全面理解染色体结构提供了至关重要的信息。染色体结构维持（SMC）家族的ATP酶蛋白是进化保守复合物的核心。SMC复合物参与调节基因组动态并维持基因组稳定性。所有SMC蛋白的结构都类似于一根细长的杆，其中包含一个中央卷曲螺旋结构域，这是一种常见的蛋白质结构基序，其中两个α螺旋相互缠绕。近年来，卷曲螺旋结构域对SMC蛋白活性和调节的重要作用已变得明显。在这里，我们讨论了SMC卷曲螺旋功能的最新进展。我们描述了SMC蛋白卷曲螺旋结构域的结构、由其介导的修饰和相互作用。此外，我们评估了卷曲螺旋结构域在SMC蛋白构象转换以及确定SMC二聚体结构中的作用。最后，我们综述了卷曲螺旋结构域中的突变与人类疾病之间的相互作用。我们认为不同SMC蛋白卷曲螺旋的独特性质有助于它们发挥不同的功能。该讨论阐明了SMC蛋白活性的潜在机制，并倡导未来开展研究以阐明SMC卷曲螺旋结构域的功能。
