Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) infects host cells through binding the receptor binding domain (RBD) on its spike glycoprotein to human receptor dipeptidyl peptidase 4 (hDPP4). Here, we report identification of critical residues on hDPP4 for RBD binding and virus entry through analysis of a panel of hDPP4 mutants. Based on the RBD–hDPP4 crystal structure we reported, the mutated residues were located at the interface between RBD and hDPP4, which potentially changed the polarity, hydrophobic or hydrophilic properties of hDPP4, thereby interfering or disrupting their interaction with RBD. Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues in hDPP4–RBD binding interface were important on hDPP4–RBD binding and viral entry. These results provide atomic insights into the features of interactions between hDPP4 and MERS-CoV RBD, and also provide potential explanation for cellular and species tropism of MERS-CoV infection. - Highlights: • It has been demonstrated that MERS-CoV infects host cells through binding its envelope spike (S) glycoprotein to the host cellular receptor dipeptidyl peptidase 4 (DPP4). • To identify the critical residues on hDPP4 for RBD binding and virus entry, we constructed a panel of hDPP4 mutants based on structure-guided mutagenesis. • Usingmore »
- Authors:
-
- Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084 (China)
- Comprehensive AIDS Research Center, Research Center for Public Health, School of Medicine, Tsinghua University, Beijing 100084 (China)
- Publication Date:
- OSTI Identifier:
- 22435079
- Resource Type:
- Journal Article
- Journal Name:
- Virology
- Additional Journal Information:
- Journal Volume: 471-473; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; AMINO ACIDS; CRYSTAL STRUCTURE; GLYCOPROTEINS; HOST; MIDDLE EAST; MUTAGENESIS; MUTANTS; RECEPTORS; RESIDUES; VIRUSES
Citation Formats
Song, Wenfei, Wang, Ying, Wang, Nianshuang, Wang, Dongli, Guo, Jianying, Fu, Lili, and Shi, Xuanling. Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry. United States: N. p., 2014.
Web. doi:10.1016/J.VIROL.2014.10.006.
Song, Wenfei, Wang, Ying, Wang, Nianshuang, Wang, Dongli, Guo, Jianying, Fu, Lili, & Shi, Xuanling. Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry. United States. https://doi.org/10.1016/J.VIROL.2014.10.006
Song, Wenfei, Wang, Ying, Wang, Nianshuang, Wang, Dongli, Guo, Jianying, Fu, Lili, and Shi, Xuanling. 2014.
"Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry". United States. https://doi.org/10.1016/J.VIROL.2014.10.006.
@article{osti_22435079,
title = {Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry},
author = {Song, Wenfei and Wang, Ying and Wang, Nianshuang and Wang, Dongli and Guo, Jianying and Fu, Lili and Shi, Xuanling},
abstractNote = {Middle East respiratory syndrome coronavirus (MERS-CoV) infects host cells through binding the receptor binding domain (RBD) on its spike glycoprotein to human receptor dipeptidyl peptidase 4 (hDPP4). Here, we report identification of critical residues on hDPP4 for RBD binding and virus entry through analysis of a panel of hDPP4 mutants. Based on the RBD–hDPP4 crystal structure we reported, the mutated residues were located at the interface between RBD and hDPP4, which potentially changed the polarity, hydrophobic or hydrophilic properties of hDPP4, thereby interfering or disrupting their interaction with RBD. Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues in hDPP4–RBD binding interface were important on hDPP4–RBD binding and viral entry. These results provide atomic insights into the features of interactions between hDPP4 and MERS-CoV RBD, and also provide potential explanation for cellular and species tropism of MERS-CoV infection. - Highlights: • It has been demonstrated that MERS-CoV infects host cells through binding its envelope spike (S) glycoprotein to the host cellular receptor dipeptidyl peptidase 4 (DPP4). • To identify the critical residues on hDPP4 for RBD binding and virus entry, we constructed a panel of hDPP4 mutants based on structure-guided mutagenesis. • Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues on hDPP4 had significant impacts on virus/receptor interactions and viral entry. • Our study has provided new insights into the features of interactions between hDPP4 and MERS-CoV RBD, and provides potential explanation for cellular and species tropism of MERS-CoV infection.},
doi = {10.1016/J.VIROL.2014.10.006},
url = {https://www.osti.gov/biblio/22435079},
journal = {Virology},
issn = {0042-6822},
number = ,
volume = 471-473,
place = {United States},
year = {Mon Dec 15 00:00:00 EST 2014},
month = {Mon Dec 15 00:00:00 EST 2014}
}