Chapter 13
Viral PDZ Binding Motifs Influence Cell Behavior Through
the Interaction with Cellular Proteins Containing PDZ
Domains
Carlos Castan ˜ o-Rodriguez, Jose M. Honrubia, Javier Gutie ´ rrez-A ´ lvarez,
Isabel Sola, and Luis Enjuanes
Abstract
Viruses have evolved to interact with their hosts. Some viruses such as human papilloma virus, dengue virus,
SARS-CoV, or influenza virus encode proteins including a PBM that interact with cellular proteins containing PDZ domains. There are more than 400 cellular protein isoforms with these domains in the human
genome, indicating that viral PBMs have a high potential to influence the behavior of the cell. In this review
we analyze the most relevant cellular processes known to be affected by viral PBM–cellular PDZ interactions
including the establishment of cell–cell interactions and cell polarity, the regulation of cell survival and
apoptosis and the activation of the immune system. Special attention has been provided to coronavirus
PBM conservation throughout evolution and to the role of the PBMs of human coronaviruses SARS-CoV
and MERS-CoV in pathogenesis.
Key words PDZ, PBM, Virus, Pathogenesis, Replication
1 Introduction
PDZ domains are protein–protein interaction sequences consisting
of 80–90 amino acids. They form a structure composed of an
antiparallel β barrel made of six β strands and two α helixes
(Fig. 1) [1]. PDZ is an acronym formed as the abbreviation of the
names of the three first proteins where this domain was identified:
postsynaptic density-95 (PSD-95), the drosophila tumor suppressor protein Dlg1 (discs large 1), and the tight junction protein
ZO-1 (zonula occludens 1) [2]. These domains can be found in
hundreds of proteins, both in eukaryotic cells and in bacteria
[3]. Up to 266 PDZ domains which are part of more than 400 different protein isoforms have been described in the human genome
[4, 5]. These proteins may include from one to thirteen PDZ
Jean-Paul Borg (ed.), PDZ Mediated Interactions: Methods and Protocols, Methods in Molecular Biology, vol. 2256,
https://doi.org/10.1007/978-1-0716-1166-1_13, © Springer Science+Business Media, LLC, part of Springer Nature 2021
217
Viral PDZ Binding Motifs Influence Cell Behavior Through
the Interaction with Cellular Proteins Containing PDZ
Domains
Carlos Castan ˜ o-Rodriguez, Jose M. Honrubia, Javier Gutie ´ rrez-A ´ lvarez,
Isabel Sola, and Luis Enjuanes
Abstract
Viruses have evolved to interact with their hosts. Some viruses such as human papilloma virus, dengue virus,
SARS-CoV, or influenza virus encode proteins including a PBM that interact with cellular proteins containing PDZ domains. There are more than 400 cellular protein isoforms with these domains in the human
genome, indicating that viral PBMs have a high potential to influence the behavior of the cell. In this review
we analyze the most relevant cellular processes known to be affected by viral PBM–cellular PDZ interactions
including the establishment of cell–cell interactions and cell polarity, the regulation of cell survival and
apoptosis and the activation of the immune system. Special attention has been provided to coronavirus
PBM conservation throughout evolution and to the role of the PBMs of human coronaviruses SARS-CoV
and MERS-CoV in pathogenesis.
Key words PDZ, PBM, Virus, Pathogenesis, Replication
1 Introduction
PDZ domains are protein–protein interaction sequences consisting
of 80–90 amino acids. They form a structure composed of an
antiparallel β barrel made of six β strands and two α helixes
(Fig. 1) [1]. PDZ is an acronym formed as the abbreviation of the
names of the three first proteins where this domain was identified:
postsynaptic density-95 (PSD-95), the drosophila tumor suppressor protein Dlg1 (discs large 1), and the tight junction protein
ZO-1 (zonula occludens 1) [2]. These domains can be found in
hundreds of proteins, both in eukaryotic cells and in bacteria
[3]. Up to 266 PDZ domains which are part of more than 400 different protein isoforms have been described in the human genome
[4, 5]. These proteins may include from one to thirteen PDZ
Jean-Paul Borg (ed.), PDZ Mediated Interactions: Methods and Protocols, Methods in Molecular Biology, vol. 2256,
https://doi.org/10.1007/978-1-0716-1166-1_13, © Springer Science+Business Media, LLC, part of Springer Nature 2021
217