Comparing the binding properties of peptides mimicking the Envelope protein of SARS-CoV and SARS-CoV-2 to the PDZ domain of the tight junction-associated PALS1 protein

Protein Sci. 2020 Oct;29(10):2038-2042. doi: 10.1002/pro.3936. Epub 2020 Sep 8.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Betacoronavirus / chemistry
  • Betacoronavirus / metabolism*
  • Binding Sites
  • COVID-19
  • Coronavirus Envelope Proteins
  • Coronavirus Infections / metabolism*
  • Coronavirus Infections / virology
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Nucleoside-Phosphate Kinase / chemistry
  • Nucleoside-Phosphate Kinase / metabolism*
  • PDZ Domains
  • Pandemics
  • Peptides / chemistry
  • Peptides / metabolism
  • Pneumonia, Viral / metabolism*
  • Pneumonia, Viral / virology
  • Protein Binding
  • SARS-CoV-2
  • Severe Acute Respiratory Syndrome / metabolism*
  • Severe Acute Respiratory Syndrome / virology
  • Severe acute respiratory syndrome-related coronavirus / chemistry
  • Severe acute respiratory syndrome-related coronavirus / metabolism*
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / metabolism*

Substances

  • Coronavirus Envelope Proteins
  • Membrane Proteins
  • Peptides
  • Viral Envelope Proteins
  • envelope protein, SARS-CoV-2
  • Nucleoside-Phosphate Kinase
  • MPP5 protein, human