RESUMO
While the COVID-19 pandemic is causing important loss of life, knowledge of the effects of the causative SARS-CoV-2 virus on human cells is currently limited. Investigating protein-protein interactions (PPIs) between viral and host proteins can provide a better understanding of the mechanisms exploited by the virus and enable the identification of potential drug targets. We therefore performed an in-depth computational analysis of the interactome of SARS-CoV-2 and human proteins in infected HEK 293 cells published by Gordon et al. (Nature2020, 583, 459-468) to reveal processes that are potentially affected by the virus and putative protein binding sites. Specifically, we performed a set of network-based functional and sequence motif enrichment analyses on SARS-CoV-2-interacting human proteins and on PPI networks generated by supplementing viral-host PPIs with known interactions. Using a novel implementation of our GoNet algorithm, we identified 329 Gene Ontology terms for which the SARS-CoV-2-interacting human proteins are significantly clustered in PPI networks. Furthermore, we present a novel protein sequence motif discovery approach, LESMoN-Pro, that identified 9 amino acid motifs for which the associated proteins are clustered in PPI networks. Together, these results provide insights into the processes and sequence motifs that are putatively implicated in SARS-CoV-2 infection and could lead to potential therapeutic targets.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Interações Hospedeiro-Patógeno/genética , Pandemias , Pneumonia Viral , Mapas de Interação de Proteínas , Algoritmos , Motivos de Aminoácidos , Betacoronavirus/química , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , COVID-19 , Análise por Conglomerados , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Ontologia Genética , Células HEK293 , Humanos , Anotação de Sequência Molecular , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Ligação Proteica , Mapas de Interação de Proteínas/genética , Mapas de Interação de Proteínas/fisiologia , Proteínas/química , Proteínas/classificação , Proteínas/genética , Proteínas/metabolismo , SARS-CoV-2 , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
Histone reader domains provide a mechanism for sensing states of coordinated nuclear processes marked by histone proteins' post-translational modifications (PTMs). Among a growing number of discovered histone readers, the 14-3-3s, ankyrin repeat domains (ARDs), tetratricopeptide repeats (TPRs), bromodomains (BRDs), and HEAT domains are a group of domains using various mechanisms to recognize unmodified or modified histones, yet they all are composed of an α-helical fold. In this review, we compare how these readers fold to create protein domains that are very diverse in their tertiary structures, giving rise to intriguing peptide binding mechanisms resulting in vastly different footprints of their targets.