Chavali Sreenivas, Singh Anjali K, Santhanam Balaji, Babu M Madan
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati, India.
Nat Rev Chem. 2020 Aug;4(8):420-434. doi: 10.1038/s41570-020-0204-1. Epub 2020 Jul 21.
Amino acid homorepeats, or homorepeats, are polypeptide segments found in proteins that contain stretches of identical amino acid residues. Although abnormal homorepeat expansions are linked to pathologies such as neurodegenerative diseases, homorepeats are prevalent in eukaryotic proteomes, suggesting that they are important for normal physiology. In this Review, we discuss recent advances in our understanding of the biological functions of homorepeats, which range from facilitating subcellular protein localization to mediating interactions between proteins across diverse cellular pathways. We explore how the functional diversity of homorepeat-containing proteins could be linked to the ability of homorepeats to adopt different structural conformations, an ability influenced by repeat composition, repeat length and the nature of flanking sequences. We conclude by highlighting how an understanding of homorepeats will help us better characterize and develop therapeutics against the human diseases to which they contribute.
氨基酸同聚重复序列，或简称同聚重复序列，是在蛋白质中发现的多肽片段，其中包含一段段相同的氨基酸残基。尽管异常的同聚重复序列扩增与神经退行性疾病等病理状况相关，但同聚重复序列在真核生物蛋白质组中普遍存在，这表明它们对正常生理功能很重要。在本综述中，我们讨论了在理解同聚重复序列生物学功能方面的最新进展，其功能范围从促进亚细胞蛋白质定位到介导不同细胞途径中蛋白质之间的相互作用。我们探讨了含同聚重复序列蛋白质的功能多样性如何与同聚重复序列采用不同结构构象的能力相关联，这种能力受重复序列组成、重复长度和侧翼序列性质的影响。我们最后强调，了解同聚重复序列将如何帮助我们更好地表征和开发针对它们所引发的人类疾病的治疗方法。
