Viral targeting of PDZ polarity proteins in the immune system as a potential evasion mechanism

Gutiérrez‐González, Luis H.; Santos‐Mendoza, Teresa

doi:10.1096/fj.201900518r

Cited by 29 publications

(31 citation statements)

References 107 publications

(139 reference statements)

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“…In the future, it will be interesting to explore whether these proteins are expressed in other leukocytes, the interactions they may establish, and the outcome of such possible interactions. Interestingly, it has been recently hypothesized that the kidnapping of PDZ proteins by viral PDZbmbearing proteins may be a common mechanism of immune evasion [70]. These possibilities make the study of PDZ polarity proteins all the more important.…”

Section: Discussionmentioning

confidence: 99%

The Scribble Complex PDZ Proteins in Immune Cell Polarities

Barreda

Gutiérrez‐González

Martínez-Cordero

et al. 2020

Journal of Immunology Research

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hScrib and hDlg belong to the PDZ family of proteins. Since the identification of these highly phylogenetically conserved scaffolds, an increasing amount of experiments has elucidated the roles of hScrib and hDlg in a variety of cell functions. Remarkably, their participation during the establishment of polarity in epithelial cells is well documented. Although the role of both proteins in the immune system is scantly known, it has become a growing field of investigation. Here, we summarize the interactions and functions of hScrib and hDlg1, which participate in diverse functions involving cell polarization in immune cells, and discuss their relevance in the immune cell biology. The fundamental role of hScrib and hDlg1 during the establishment of the immunological synapse, hence T cell activation, and the recently described role of hScrib in reactive oxygen species production in macrophages and of hDlg1 in cytokine production by dendritic cells highlight the importance of both proteins in immune cell biology. The expression of these proteins in other leukocytes can be anticipated and needs to be confirmed. Due to their multiple interaction domains, there is a wide range of possible interactions of hScrib and hDlg1 that remains to be explored in the immune system.

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Section: Discussionmentioning

confidence: 99%

The Scribble Complex PDZ Proteins in Immune Cell Polarities

Barreda

Gutiérrez‐González

Martínez-Cordero

et al. 2020

Journal of Immunology Research

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“…This feature is exerted by displaying short linear motifs, interacting with cellular proteins. Among these types of protein–protein recognition modules, PDZ domains represent a frequent target of viral systems, ranging from HPV, adenoviruses, rabies to influenza 4,5 . These viruses display PDZ binding motifs (PBM) that bind specific cellular PDZ domain proteins, thereby jeopardizing the function of these proteins.…”

Section: Figurementioning

confidence: 99%

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

Toto

Malagrinò

et al. 2020

Protein Science

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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.

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“…Targeting host proteins from polarity and junctions complexes may have a consequence on the morphology of epithelium/endothelium but also on the immune response and cellular homeostasis [40]. In addition to their structural role in many tissues and organs, they can also regulate signaling mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Host PDZ-containing proteins targeted by SARS-Cov-2

Caillet‐Saguy

Durbesson

Rezelj

et al. 2021

Preprint

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Small linear motif targeting protein interacting domains called PDZ have been identified at the C-terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins E, 3a, and N. Using a high-throughput approach of affinity-profiling against the full human PDZome, we identified sixteen human PDZ binders of SARS-CoV-2 proteins E, 3A and N showing significant interactions with dissociation constants values ranging from 3 μM to 82 μM. Six of them (TJP1, PTPN13, HTRA1, PARD3, MLLT4, LNX2) are also recognized by SARS-CoV while three (NHERF1, MAST2, RADIL) are specific to SARS-CoV-2 E protein. Most of these SARS-CoV-2 protein partners are involved in cellular junctions/polarity and could be also linked to evasion mechanisms of the immune responses during viral infection. Seven of the PDZ-containing proteins among binders of the SARS-CoV-2 proteins E, 3a or N affect significantly viral replication under knock-down gene expression in infected cells. This PDZ profiling identifying human proteins potentially targeted by SARS-CoV-2 can help to understand the multifactorial severity of COVID19 and to conceive effective anti-coronaviral agents for therapeutic purposes.

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Viral targeting of PDZ polarity proteins in the immune system as a potential evasion mechanism

Cited by 29 publications

References 107 publications

The Scribble Complex PDZ Proteins in Immune Cell Polarities

The Scribble Complex PDZ Proteins in Immune Cell Polarities

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

Host PDZ-containing proteins targeted by SARS-Cov-2

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