TY - JOUR
T1 - Pathogens use structural mimicry of native host ligands as a mechanism for host receptor engagement
AU - Drayman, Nir
AU - Glick, Yair
AU - Ben-Nun-Shaul, Orly
AU - Zer, Hagit
AU - Zlotnick, Adam
AU - Gerber, Doron
AU - Schueler-Furman, Ora
AU - Oppenheim, Ariella
N1 - 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.
PY - 2013/7/17
Y1 - 2013/7/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84880398090&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.chom.2013.05.005
DO - https://doi.org/10.1016/j.chom.2013.05.005
M3 - مقالة
C2 - 23870314
SN - 1931-3128
VL - 14
SP - 63
EP - 73
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 1
ER -