Attwood Misty M, Schiöth Helgi B
Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
Front Cell Dev Biol. 2020 Jan 22;7:386. doi: 10.3389/fcell.2019.00386. eCollection 2019.
As the structure and functions of proteins are correlated, investigating groups of proteins with the same gross structure may provide important insights about their functional roles. Trispanins, proteins that contain three alpha-helical transmembrane (3TM) regions, have not been previously studied considering their transmembrane features. Our comprehensive identification and classification using bioinformatic methods describe 152 3TM proteins. These proteins are frequently involved in membrane biosynthesis and lipid biogenesis, protein trafficking, catabolic processes, and in particular signal transduction due to the large ionotropic glutamate receptor family. Proteins that localize to intracellular compartments are overrepresented in the dataset in comparison to the entire human transmembrane proteome, and nearly 45% localize specifically to the endoplasmic reticulum (ER). Furthermore, nearly 20% of the trispanins function in lipid metabolic processes and transport, which are also overrepresented. Nearly one-third of trispanins are identified as being targeted by drugs and/or being associated with diseases. A high number of 3TMs have unknown functions and based on this analysis we speculate on the functional involvement of uncharacterized trispanins in relationship to disease or important cellular activities. This first overall study of trispanins provides a unique analysis of a diverse group of membrane proteins.
由于蛋白质的结构与功能相互关联，研究具有相同总体结构的蛋白质组可能会为其功能作用提供重要见解。跨膜三联蛋白是一类含有三个α螺旋跨膜（3TM）区域的蛋白质，此前尚未从其跨膜特征的角度进行研究。我们使用生物信息学方法进行的全面鉴定和分类描述了152种3TM蛋白质。这些蛋白质频繁参与膜生物合成和脂质生物合成、蛋白质运输、分解代谢过程，特别是由于离子型谷氨酸受体大家族的存在而参与信号转导。与整个人类跨膜蛋白质组相比，定位于细胞内区室的蛋白质在数据集中的占比过高，近45%的蛋白质特异性定位于内质网（ER）。此外，近20%的跨膜三联蛋白在脂质代谢过程和运输中发挥作用，这一比例也过高。近三分之一的跨膜三联蛋白被确定为药物作用靶点和/或与疾病相关。大量的3TM具有未知功能，基于此分析，我们推测未表征的跨膜三联蛋白在疾病或重要细胞活动中的功能参与情况。这项对跨膜三联蛋白的首次全面研究对一组多样的膜蛋白进行了独特分析。
