Abstract
The Envelope protein (E) is one of the four structural proteins encoded by the genome of SARS-CoV and SARS-CoV-2 Coronaviruses. It is an integral membrane protein, highly expressed in the host cell, which is known to have an important role in Coronaviruses maturation, assembly and virulence. The E protein presents a PDZ-binding motif at its C-terminus. One of the key interactors of the E protein in the intracellular environment is the PDZ containing protein PALS1. This interaction is known to play a key role in the SARS-CoV pathology and suspected to affect the integrity of the lung epithelia. In this paper we measured and compared the affinity of peptides mimicking the E protein from SARS-CoV and SARS-CoV-2 for the PDZ domain of PALS1, through equilibrium and kinetic binding experiments. Our results support the hypothesis that the increased virulence of SARS-CoV-2 compared to SARS-CoV may rely on the increased affinity of its Envelope protein for PALS1.
Keywords:
PALS1; PDZ; SARS-CoV-2; binding; envelope protein; kinetics.
© 2020 The Protein Society.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Betacoronavirus / chemistry
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Betacoronavirus / metabolism*
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Binding Sites
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COVID-19
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Coronavirus Envelope Proteins
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Coronavirus Infections / metabolism*
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Coronavirus Infections / virology
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Humans
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Membrane Proteins / chemistry
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Membrane Proteins / metabolism*
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Models, Molecular
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Nucleoside-Phosphate Kinase / chemistry
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Nucleoside-Phosphate Kinase / metabolism*
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PDZ Domains
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Pandemics
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Peptides / chemistry
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Peptides / metabolism
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Pneumonia, Viral / metabolism*
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Pneumonia, Viral / virology
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Protein Binding
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SARS-CoV-2
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Severe Acute Respiratory Syndrome / metabolism*
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Severe Acute Respiratory Syndrome / virology
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Severe acute respiratory syndrome-related coronavirus / chemistry
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Severe acute respiratory syndrome-related coronavirus / metabolism*
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Viral Envelope Proteins / chemistry
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Viral Envelope Proteins / metabolism*
Substances
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Coronavirus Envelope Proteins
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Membrane Proteins
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Peptides
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Viral Envelope Proteins
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envelope protein, SARS-CoV-2
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Nucleoside-Phosphate Kinase
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MPP5 protein, human