German Center for Neurodegenerative Diseases (DZNE), Translational Structural Biology, Göttingen, Germany.
Department of Biotechnology, University of Verona, Verona, Italy.
Protein Sci. 2024 Jul;33(7):e5079. doi: 10.1002/pro.5079.
Heterochromatin protein 1 alpha (HP1α) is an evolutionarily conserved protein that binds chromatin and is important for gene silencing. The protein comprises 191 residues arranged into three disordered regions and two structured domains, the chromo and chromoshadow domain, which associates into a homodimer. While high-resolution structures of the isolated domains of HP1 proteins are known, the structural properties of full-length HP1α remain largely unknown. Using a combination of NMR spectroscopy and structure predictions by AlphaFold2 we provide evidence that the chromo and chromoshadow domain of HP1α engage in direct contacts resulting in a compact chromo/chromoshadow domain arrangement. We further show that HP1β and HP1γ have increased interdomain dynamics when compared to HP1α which may contribute to the distinct roles of different Hp1 isoforms in gene silencing and activation.
异染色质蛋白 1 阿尔法 (HP1α) 是一种进化上保守的蛋白质，可结合染色质，对于基因沉默非常重要。该蛋白质由 191 个残基组成，排列成三个无序区域和两个结构域，即染色质和染色质阴影域，它们可形成同源二聚体。尽管已知 HP1 蛋白的孤立结构域的高分辨率结构，但全长 HP1α 的结构特性在很大程度上仍未知。通过使用 NMR 光谱学和 AlphaFold2 的结构预测相结合，我们提供了证据表明 HP1α 的染色质和染色质阴影域之间存在直接接触，从而导致紧凑的染色质/染色质阴影域排列。我们进一步表明，与 HP1α 相比，HP1β 和 HP1γ 的结构域间动力学增加，这可能有助于不同 Hp1 同工型在基因沉默和激活中发挥不同作用。
