Elkhaligy Heidy, Balbin Christian A, Siltberg-Liberles Jessica
Department of Biological Sciences, Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA.
Pathogens. 2022 May 15;11(5):583. doi: 10.3390/pathogens11050583.
Protein-protein interactions drive functions in eukaryotes that can be described by short linear motifs (SLiMs). Conservation of SLiMs help illuminate functional SLiMs in eukaryotic protein families. However, the simplicity of eukaryotic SLiMs makes them appear by chance due to mutational processes not only in eukaryotes but also in pathogenic bacteria and viruses. Further, functional eukaryotic SLiMs are often found in disordered regions. Although proteomes from pathogenic bacteria and viruses have less disorder than eukaryotic proteomes, their proteins can successfully mimic eukaryotic SLiMs and disrupt host cellular function. Identifying important SLiMs in pathogens is difficult but essential for understanding potential host-pathogen interactions. We performed a comparative analysis of structural features for experimentally verified SLiMs from the Eukaryotic Linear Motif (ELM) database across viruses, bacteria, and eukaryotes. Our results revealed that many viral SLiMs and specific motifs found across viruses and eukaryotes, such as some glycosylation motifs, have less disorder. Analyzing the disorder and coil properties of equivalent SLiMs from pathogens and eukaryotes revealed that some motifs are more structured in pathogens than their eukaryotic counterparts and vice versa. These results support a varying mechanism of interaction between pathogens and their eukaryotic hosts for some of the same motifs.
蛋白质-蛋白质相互作用驱动真核生物中的各种功能，这些功能可以由短线性基序（SLiMs）来描述。SLiMs的保守性有助于揭示真核生物蛋白质家族中的功能性SLiMs。然而，真核生物SLiMs的简单性使其不仅在真核生物中，而且在致病细菌和病毒中由于突变过程而偶然出现。此外，功能性真核生物SLiMs通常存在于无序区域。尽管致病细菌和病毒的蛋白质组比真核生物蛋白质组的无序程度低，但其蛋白质可以成功模拟真核生物SLiMs并破坏宿主细胞功能。识别病原体中重要的SLiMs很困难，但对于理解潜在的宿主-病原体相互作用至关重要。我们对来自真核线性基序（ELM）数据库的经实验验证的SLiMs在病毒、细菌和真核生物中的结构特征进行了比较分析。我们的结果表明，许多病毒SLiMs以及在病毒和真核生物中发现的特定基序，如一些糖基化基序，无序程度较低。分析来自病原体和真核生物的等效SLiMs的无序和卷曲特性表明，一些基序在病原体中比在其真核生物对应物中结构更紧密，反之亦然。这些结果支持了病原体与其真核宿主之间对于某些相同基序存在不同的相互作用机制。
