Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
Graduate Program in Biochemistry, Tufts School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, USA.
mBio. 2020 May 5;11(3):e00810-20. doi: 10.1128/mBio.00810-20.
A distinguishing morphological feature of all herpesviruses is the multiprotein tegument layer located between the nucleocapsid and lipid envelope of the virion. Tegument proteins play multiple roles in viral replication, including viral assembly, but we do not yet understand their individual functions or how the tegument is assembled and organized. UL11, the smallest tegument protein, is important for several distinct processes in replication, including efficient virion morphogenesis and cell-cell spread. However, the mechanistic understanding of its role in these and other processes is limited in part by the scant knowledge of its biochemical and structural properties. Here, we report that UL11 from herpes simplex virus 1 (HSV-1) is an intrinsically disordered, conformationally dynamic protein that undergoes liquid-liquid phase separation (LLPS) Intrinsic disorder may underlie the ability of UL11 to exert multiple functions and bind multiple partners. Sequence analysis suggests that not only all UL11 homologs but also all HSV-1 tegument proteins contain intrinsically disordered regions of different lengths. The presence of intrinsic disorder, and potentially, the ability to form LLPS, may thus be a common feature of the tegument proteins. We hypothesize that tegument assembly may involve the formation of a biomolecular condensate, driven by the heterogeneous mixture of intrinsically disordered tegument proteins. Herpesvirus virions contain a unique tegument layer sandwiched between the capsid and lipid envelope and composed of multiple copies of about two dozen viral proteins. However, little is known about the structure of the tegument or how it is assembled. Here, we show that a conserved tegument protein UL11 from herpes simplex virus 1, a prototypical alphaherpesvirus, is an intrinsically disordered protein that undergoes liquid-liquid phase separation Through sequence analysis, we find intrinsically disordered regions of different lengths in all HSV-1 tegument proteins. We hypothesize that intrinsic disorder is a common characteristic of tegument proteins and propose a new model of tegument as a biomolecular condensate.
所有疱疹病毒的一个显著形态特征是位于病毒衣壳和脂质包膜之间的多蛋白被膜层。被膜蛋白在病毒复制过程中发挥多种作用，包括病毒组装，但我们还不完全了解它们各自的功能，也不了解被膜是如何组装和组织的。最小的被膜蛋白 UL11 对复制过程中的几个不同过程都很重要，包括有效形成病毒形态和细胞间传播。然而，由于对其生化和结构特性的了解甚少，因此其在这些和其他过程中的作用的机制理解受到限制。在这里，我们报告说，单纯疱疹病毒 1 (HSV-1) 的 UL11 是一种固有无序、构象动态的蛋白质，它会发生液-液相分离 (LLPS)。固有无序可能是 UL11 发挥多种功能和结合多个伴侣的基础。序列分析表明，不仅所有 UL11 同源物，而且所有 HSV-1 被膜蛋白都含有不同长度的固有无序区域。因此，固有无序的存在，以及可能形成 LLPS 的能力，可能是被膜蛋白的一个共同特征。我们假设被膜组装可能涉及由固有无序的被膜蛋白的异质混合物驱动的生物分子凝聚物的形成。疱疹病毒病毒粒子包含一个独特的被膜层，夹在衣壳和脂质包膜之间，由大约二十几种病毒蛋白的多个拷贝组成。然而，关于被膜的结构或其组装方式知之甚少。在这里，我们表明，单纯疱疹病毒 1 的一种保守被膜蛋白 UL11 是一种固有无序的蛋白质，它会发生液-液相分离。通过序列分析，我们在所有 HSV-1 被膜蛋白中发现了不同长度的固有无序区域。我们假设固有无序是被膜蛋白的一个共同特征，并提出了一个新的被膜模型，即生物分子凝聚物。
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