Chen Kelan, Czabotar Peter E, Blewitt Marnie E, Murphy James M
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia
Biochem J. 2016 Mar 15;473(6):733-42. doi: 10.1042/BJ20151049. Epub 2016 Jan 5.
The structural maintenance of chromosomes (SMC) proteins are fundamental to chromosome organization. They share a characteristic domain structure, featuring a central SMC hinge domain that is critical for forming SMC dimers and interacting with nucleic acids. The structural maintenance of chromosomes flexible hinge domain containing 1 (Smchd1) is a non-canonical member of the SMC family. Although it has been well established that Smchd1 serves crucial roles in epigenetic silencing events implicated in development and disease, much less is known about the structure and function of the Smchd1 protein. Recently, we demonstrated that the C-terminal hinge domain of Smchd1 forms a nucleic acid-binding homodimer; however, it is unclear how the protomers are assembled within the hinge homodimer and how the full-length Smchd1 protein is organized with respect to the hinge region. In the present study, by employing SAXS we demonstrate that the hinge domain of Smchd1 probably adopts an unconventional homodimeric arrangement augmented by an intermolecular coiled coil formed between the two monomers. Such a dimeric structure differs markedly from that of archetypical SMC proteins, raising the possibility that Smchd1 binds chromatin in an unconventional manner.
染色体结构维持（SMC）蛋白对于染色体组织至关重要。它们具有特征性的结构域结构，其核心是SMC铰链结构域，该结构域对于形成SMC二聚体以及与核酸相互作用至关重要。含染色体结构维持柔性铰链结构域1（Smchd1）是SMC家族的非典型成员。尽管已经充分证实Smchd1在与发育和疾病相关的表观遗传沉默事件中发挥关键作用，但对于Smchd1蛋白的结构和功能却知之甚少。最近，我们证明Smchd1的C端铰链结构域形成核酸结合同源二聚体；然而，尚不清楚原聚体在铰链同源二聚体内如何组装，以及全长Smchd1蛋白相对于铰链区域是如何组织的。在本研究中，通过使用小角X射线散射（SAXS），我们证明Smchd1的铰链结构域可能采用一种非常规的同源二聚体排列方式，这种排列通过两个单体之间形成的分子间卷曲螺旋得到增强。这种二聚体结构与典型的SMC蛋白明显不同，这增加了Smchd1以非常规方式结合染色质的可能性。
