Dynamic, but Not Necessarily Disordered, Human-Virus Interactions Mediated through SLiMs in Viral Proteins

Viruses. 2021 Nov 26;13(12):2369. doi: 10.3390/v13122369.

Abstract

Most viruses have small genomes that encode proteins needed to perform essential enzymatic functions. Across virus families, primary enzyme functions are under functional constraint; however, secondary functions mediated by exposed protein surfaces that promote interactions with the host proteins may be less constrained. Viruses often form transient interactions with host proteins through conformationally flexible interfaces. Exposed flexible amino acid residues are known to evolve rapidly suggesting that secondary functions may generate diverse interaction potentials between viruses within the same viral family. One mechanism of interaction is viral mimicry through short linear motifs (SLiMs) that act as functional signatures in host proteins. Viral SLiMs display specific patterns of adjacent amino acids that resemble their host SLiMs and may occur by chance numerous times in viral proteins due to mutational and selective processes. Through mimicry of SLiMs in the host cell proteome, viruses can interfere with the protein interaction network of the host and utilize the host-cell machinery to their benefit. The overlap between rapidly evolving protein regions and the location of functionally critical SLiMs suggest that these motifs and their functional potential may be rapidly rewired causing variation in pathogenicity, infectivity, and virulence of related viruses. The following review provides an overview of known viral SLiMs with select examples of their role in the life cycle of a virus, and a discussion of the structural properties of experimentally validated SLiMs highlighting that a large portion of known viral SLiMs are devoid of predicted intrinsic disorder based on the viral SLiMs from the ELM database.

Keywords: SLiMs; intrinsically disordered protein regions; short eukaryotic linear motifs; the ELM database; viral-host protein interaction.

Publication types

  • Review

MeSH terms

  • Amino Acid Motifs
  • Databases, Protein
  • Host-Pathogen Interactions*
  • Humans
  • Intrinsically Disordered Proteins / genetics
  • Intrinsically Disordered Proteins / metabolism*
  • Protein Interaction Maps
  • Proteome
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Viruses / genetics

Substances

  • Intrinsically Disordered Proteins
  • Proteome
  • Viral Proteins