Capelluto Daniel G S
Protein Signaling Domains Laboratory, Department of Biological Sciences, Fralin Life Sciences Institute, Center for Soft Matter and Biological Physics, Virginia Tech, Blacksburg, VA, United States.
Front Mol Biosci. 2022 Nov 30;9:1080161. doi: 10.3389/fmolb.2022.1080161. eCollection 2022.
Sulfatide is an abundant glycosphingolipid in the mammalian nervous system, kidney, trachea, gastrointestinal tract, spleen, and pancreas and is found in low levels in other tissues. Sulfatide is characterized by the presence of a sulfate group in the hydrophilic galactose moiety, with isoforms differing in their sphingosine base and the length, unsaturation, and hydroxylation of their acyl chain. Sulfatide has been associated with a variety of cellular processes including immune responses, cell survival, myelin organization, platelet aggregation, and host-pathogen interactions. Structural studies of protein-sulfatide interactions markedly advanced our understanding of their molecular contacts, key-interacting residues, orientation of the sulfatide in its binding site, and in some cases, sulfatide-mediated protein oligomerization. To date, all protein-sulfatide interactions are reported to display dissociation constants in the low micromolar range. At least three distinct modes of protein-sulfatide binding were identified: 1) protein binding to short consensus stretches of amino acids that adopt α-helical-loop-α-helical conformations; 2) sulfatide-bound proteins that present the sulfatide head group to another protein; and 3) proteins that cage sulfatides. The scope of this review is to present an up-to-date overview of these molecular mechanisms of sulfatide recognition to better understand the role of this glycosphingolipid in physiological and pathological states.
硫苷脂是哺乳动物神经系统、肾脏、气管、胃肠道、脾脏和胰腺中含量丰富的糖鞘脂，在其他组织中含量较低。硫苷脂的特征是在亲水性半乳糖部分存在硫酸基团，其异构体在鞘氨醇碱基以及酰基链的长度、不饱和度和羟基化方面存在差异。硫苷脂与多种细胞过程相关，包括免疫反应、细胞存活、髓鞘组织形成、血小板聚集和宿主 - 病原体相互作用。蛋白质 - 硫苷脂相互作用的结构研究显著推进了我们对它们分子接触、关键相互作用残基、硫苷脂在其结合位点的取向的理解，并且在某些情况下，推进了对硫苷脂介导的蛋白质寡聚化的理解。迄今为止，所有报道的蛋白质 - 硫苷脂相互作用的解离常数都在低微摩尔范围内。已确定至少三种不同的蛋白质 - 硫苷脂结合模式：1）蛋白质与采用α - 螺旋 - 环 - α - 螺旋构象的短氨基酸共有序列结合；2）将硫苷脂头部基团呈现给另一种蛋白质的硫苷脂结合蛋白；3）包裹硫苷脂的蛋白质。本综述的范围是对硫苷脂识别的这些分子机制进行最新概述，以更好地理解这种糖鞘脂在生理和病理状态中的作用。
