title: Pathogens use structural mimicry of native host ligands as a mechanism for host receptor engagement.
abstract: 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.
authors.affiliation: Department of Haematology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Drayman
authors.forename: Yair
authors.initials: Y
authors.lastname: Glick
authors.forename: Orly
authors.initials: O
authors.lastname: Ben-nun-shaul
authors.forename: Hagit
authors.initials: H
authors.lastname: Zer
authors.forename: Adam
authors.initials: A
authors.lastname: Zlotnick
authors.forename: Doron
authors.initials: D
authors.lastname: Gerber
authors.forename: Ora
authors.initials: O
authors.lastname: Schueler-Furman
authors.forename: Ariella
authors.initials: A
authors.lastname: Oppenheim
mesh_terms: D000465:Algorithms; D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D001424:Bacterial Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014777:Virus Diseases / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D014780:Viruses / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D011956:Receptors, Cell Surface; D011991:Receptors, Virus