Resources to Discover and Use Short Linear Motifs in Viral Proteins

Abstract

Viral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Motif mimicry tolerates mutations, evolves quickly to modify interactions with the host, and enables modular interactions with protein complexes. Host cells cannot easily coordinate changes to conserved motif recognition and binding interfaces under selective pressure to maintain critical signaling pathways. SLiMs offer potential for use in synthetic biology, such as better immunogens and therapies, but may also present biosecurity challenges. We survey viral uses of SLiMs to mimic host proteins, and information resources available for motif discovery. As the number of examples continues to grow, knowledge management tools are essential to help organize and compare new findings.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope (E) protein harbors a conserved BH3-like sequence

“…from several unrelated microbial species: DNA viruses (HHV8, HBV, HCV), RNA viruses (e..g. Newcastle disease virus) and bacteria (Photorhabdus luminescens). The evolution of BH3 motifs appears to involve processes of divergent evolution, transfer events and random/convergent evolution (24), including possibly through viral mimicry as previously suggested for other SLiMs (27,28). Elaborating on previous works (24,29), we provide containing proteins (29).…”

“…Moreover, viral mimics often bear distant resemblance to host SLiMs (27,28). We used which provides evidence that their BH3-like region is more distantly related to the reference ZJ01 sequence than the homologous region from alpha-and deltacoronaviruses.…”

“…7, right). It is tempting to speculate that SARS-CoV-2 may exploit both types of BH3s, cellular and viral (based on linear motif mimicry) (27,28,60), to modulate host immune responses.…”

Systems Biology Approach to Characterize Potential SARS-CoV-2 Pathways Based on Protein Functional Motifs

“…The functional motifs in the coronavirus proteomes identified using exact text-finding (mining) implemented in Shetti and Shetti-Motif tools, for detailed method [6], in addition to in-house scripts, which can be supported upon request, https://sites.google.com/site/haithamsobhy/software. For short, we used the datasets of functional motifs that experimentally validated to be involved in viral infection and virulence, see reviews [7][8][9]. Additional protein domains were downloaded from PROSITE database (https://prosite.expasy.org/).…”

“…Although the high rate of homology of CoV genomes, introduction of few nucleotides may lead to significant changes on the short protein motifs or domains. Particularly, the newly isolated viruses (despite of evolutionary relationships with other CoVs) may encode new proteins of unknown functions and utilize different molecular interactions and pathways within the host cell [5][6][7][8][9]. These domains could contribute in viral virulence and ability to infect wide-range of host cells.…”