Pathogens Use Structural Mimicry of Native Host Ligands as a Mechanism for Host Receptor Engagement

A pathogen’s ability to engage host receptors is a critical determinant of its host range and interspecies transmissibility, key issues for understanding emerging diseases. However, the identification of host receptors, which are also attractive drug targets, remains a major challenge. Our structura...

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Bibliographic Details
Published in:Cell host & microbe 2013-07, Vol.14 (1), p.63-73
Main Authors: Drayman, Nir, Glick, Yair, Ben-nun-Shaul, Orly, Zer, Hagit, Zlotnick, Adam, Gerber, Doron, Schueler-Furman, Ora, Oppenheim, Ariella
Format: Article
Language:English
Subjects:
Algorithms
Animals
Bacteria - genetics
Bacteria - metabolism
Bacterial Infections - genetics
Bacterial Infections - metabolism
Bacterial Infections - microbiology
Host-Pathogen Interactions
Humans
Ligands
Models, Molecular
Protein Binding
Receptors, Cell Surface - chemistry
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Receptors, Virus - chemistry
Receptors, Virus - genetics
Receptors, Virus - metabolism
Sequence Homology, Amino Acid
Virus Diseases - genetics
Virus Diseases - metabolism
Virus Diseases - virology
Viruses - genetics
Viruses - metabolism
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Summary:A pathogen’s ability to engage host receptors is a critical determinant of its host range and interspecies transmissibility, key issues for understanding emerging diseases. However, the identification of host receptors, which are also attractive drug targets, remains a major challenge. Our structural bioinformatics studies reveal that both bacterial and viral pathogens have evolved to structurally mimic native host ligands (ligand mimicry), thus enabling engagement of their cognate host receptors. In contrast to the structural homology, amino acid sequence similarity between pathogen molecules and the mimicked host ligands was low. We illustrate the utility of this concept to identify pathogen receptors by delineating receptor tyrosine kinase Axl as a candidate receptor for the polyomavirus SV40. The SV40-Axl interaction was validated, and its participation in the infection process was verified. Our results suggest that ligand mimicry is widespread, and we present a quick tool to screen for pathogen-host receptor interactions. •Bacteria and viruses structurally mimic host ligands to interact with host receptors•Ligand mimicry provides a rapid way to screen for host receptors of pathogens•SV40 uses TAM receptors for cell recognition and the infection process
ISSN:1931-3128
1934-6069
DOI:10.1016/j.chom.2013.05.005