Rapidly evolving viral motifs mostly target biophysically constrained binding pockets of host proteins

Gal Shuler, Tzachi Hagai

Research output: Contribution to journalArticlepeer-review


Evolutionary changes in host-virus interactions can alter the course of infection, but the biophysical and regulatory constraints that shape interface evolution remain largely unexplored. Here, we focus on viral mimicry of host-like motifs that allow binding to host domains and modulation of cellular pathways. We observe that motifs from unrelated viruses preferentially target conserved, widely expressed, and highly connected host proteins, enriched with regulatory and essential functions. The interface residues within these host domains are more conserved and bind a larger number of cellular proteins than similar motif-binding domains that are not known to interact with viruses. In contrast, rapidly evolving viral-binding human proteins form few interactions with other cellular proteins and display high tissue specificity, and their interfaces have few inter-residue contacts. Our results distinguish between conserved and rapidly evolving host-virus interfaces and show how various factors limit host capacity to evolve, allowing for efficient viral subversion of host machineries.

Original languageEnglish
Article number111212
JournalCell Reports
Issue number7
StatePublished - 16 Aug 2022


  • CP: Microbiology
  • domain-motif interactions
  • host-virus co-evolution
  • host-virus interactions
  • intrinsically disordered regions
  • protein-protein interactions
  • short linear motifs
  • viral mimicry

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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