Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA.
J Biol Chem. 2021 Jan-Jun;296:100556. doi: 10.1016/j.jbc.2021.100556. Epub 2021 Mar 18.
Structures deposited in the Protein Data Bank (PDB) facilitate our understanding of many biological processes including those that fall under the general category of glycobiology. However, structure-based studies of how glycans affect protein structure, how they are synthesized, and how they regulate other biological processes remain challenging. Despite the abundant presence of glycans on proteins and the dense layers of glycans that surround most of our cells, structures containing glycans are underrepresented in the PDB. There are sound reasons for this, including difficulties in producing proteins with well-defined glycosylation and the tendency of mobile and heterogeneous glycans to inhibit crystallization. Nevertheless, the structures we do find in the PDB, even some of the earliest deposited structures, have had an impact on our understanding of function. I highlight a few examples in this review and point to some promises for the future. Promises include new structures from methodologies, such as cryo-EM, that are less affected by the presence of glycans and experiment-aided computational methods that build on existing structures to provide insight into the many ways glycans affect biological function.
储存在蛋白质数据库 (PDB) 中的结构有助于我们理解许多生物学过程,包括那些属于糖生物学范畴的过程。然而,基于结构的研究,如聚糖如何影响蛋白质结构、它们如何合成以及它们如何调节其他生物学过程,仍然具有挑战性。尽管蛋白质上存在大量的聚糖,而且我们的大多数细胞周围都有密集的聚糖层,但 PDB 中含有聚糖的结构代表性不足。造成这种情况的原因有很多,包括难以生产具有明确糖基化的蛋白质,以及移动和异质聚糖抑制结晶的倾向。然而,我们在 PDB 中发现的结构,即使是一些最早储存的结构,也对我们理解功能产生了影响。在这篇综述中,我强调了几个例子,并指出了一些未来的发展方向。这些发展方向包括来自 cryo-EM 等方法的新结构,这些结构受聚糖的影响较小,以及基于现有结构的实验辅助计算方法,这些方法为聚糖影响生物功能的多种方式提供了深入的了解。