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Literature detail

Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry.

Wenfei Song1 Ying Wang2 Nianshuang Wang1 Dongli Wang1 Jianying Guo2 Lili Fu2 Xuanling Shi3
Affiliations 3 institutions
  1. Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  2. Comprehensive AIDS Research Center, Research Center for Public Health, School of Medicine, Tsinghua University, Beijing 100084, China.
  3. Comprehensive AIDS Research Center, Research Center for Public Health, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: [email protected].
PMID 25461530 2014 Virology eng ppublish
PubMed DOI Browse context

Article

Publication summary

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.

Amino-acid residue substitution hDPP4 MERS-CoV RBD Virus Internalization Amino Acid Sequence Animals Cell Line Dipeptidyl Peptidase 4 Gene Expression Regulation, Viral Humans Insecta Middle East Respiratory Syndrome Coronavirus Models, Molecular Molecular Sequence Data Protein Conformation DPP4 protein, human

Structured evidence records

Evidence records

2 total
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Critical amino acid residues on human DPP4 determine interaction with the MERS-CoV spike RBD, influencing viral binding, entry, and species tropism.

Virus
MERS-CoV
Host
Not specified
Location
Not specified
Supporting text

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 ... 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.

Genes or proteins
spike; RBD; DPP4
Receptors
DPP4
Mechanism types
receptor_binding; cell_entry; tissue_tropism
Receptor Usage 1 records
Receptor Usage Extraction confidence 1.00
Key finding

Critical residues on human dipeptidyl peptidase 4 (DPP4) were identified as essential for MERS-CoV spike RBD binding and receptor-mediated cell entry.

Virus
MERS-CoV
Location
Not specified
Supporting text

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.

Method
surface plasmon resonance (SPR) binding analysis; pseudovirus infection assay
Receptors
dipeptidyl peptidase 4 (hDPP4)