Schoeman, D.; Cloete, R.; Fielding, B.C. The Flexible, Extended Coil of the PDZ-Binding Motif of the Three Deadly Human Coronavirus E Proteins Plays a Role in Pathogenicity. Viruses2022, 14, 1707.
Schoeman, D.; Cloete, R.; Fielding, B.C. The Flexible, Extended Coil of the PDZ-Binding Motif of the Three Deadly Human Coronavirus E Proteins Plays a Role in Pathogenicity. Viruses 2022, 14, 1707.
Schoeman, D.; Cloete, R.; Fielding, B.C. The Flexible, Extended Coil of the PDZ-Binding Motif of the Three Deadly Human Coronavirus E Proteins Plays a Role in Pathogenicity. Viruses2022, 14, 1707.
Schoeman, D.; Cloete, R.; Fielding, B.C. The Flexible, Extended Coil of the PDZ-Binding Motif of the Three Deadly Human Coronavirus E Proteins Plays a Role in Pathogenicity. Viruses 2022, 14, 1707.
Abstract
The less virulent human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 cause mild, self-limiting respiratory tract infections, while the more virulent SARS-CoV-1, MERS-CoV, and SARS-CoV-2 have caused severe outbreaks. The CoV envelope (E) protein, an important contributor to the pathogenesis of severe hCoVs infections, may provide insight into this disparate severity of the disease. We, therefore, generated full-length E protein models for SARS-CoV-1, -2, MERS-CoV, HCoV-229E, and HCoV-NL63 and docked C-terminal peptides of each model to the PDZ domain of the human PALS1 protein. The PDZ-binding motif (PBM) of the SARS-CoV-1, -2, and MERS-CoV models adopted a more flexible, extended coil while the HCoV-229E and HCoV-NL63 models adopted a less flexible alpha helix. All the E peptides docked to PALS1 occupied the same binding site and the more virulent hCoV E peptides generally interacted more stably with PALS1 than the less virulent ones. We propose that the increased flexibility of the PBM in more virulent hCoVs may permit more stable binding to various host proteins, thereby possibly contributing to more severe disease. This is the first paper to model full-length 3D structures for both more virulent and less virulent hCoVs E proteins, providing novel insights for possible drug and/or vaccine development.
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