Pathogens use structural mimicry of native host ligands as a mechanism for host receptor engagement

Nir Drayman, Yair Glick, Orly Ben-Nun-Shaul, Hagit Zer, Adam Zlotnick, Doron Gerber, Ora Schueler-Furman, Ariella Oppenheim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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.

Original languageAmerican English
Pages (from-to)63-73
Number of pages11
JournalCell Host and Microbe
Volume14
Issue number1
DOIs
StatePublished - 17 Jul 2013

Bibliographical note

Funding Information:
We wish to thank Yinon Ben-Neriah, Oren Kobiler, Riki Perlman, Dori Filon, and Eitan Schechtman for helpful discussions and critical reading of the manuscript. This project is supported by the ISRAELI SCIENCE FOUNDATION (grant 291/12) and the United States-Israel Binational Science Foundation (BSF) (grant 2005050). N.D. is a recipient of the Harry and Silvia Hoffman leadership program fellowship. This research project was supported in part by a grant from USAID’s American Schools and Hospitals Abroad (ASHA) Program for the procurement of the LSM 710 confocal microscope.

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