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Protein-Protein Interactions of Viroporins in Coronaviruses and Paramyxoviruses: New Targets for Antivirals?

Torres J, Surya W, Li Y, Liu DX - Viruses (2015)

Bottom Line: The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail.In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains.These should complement current efforts to block viroporin channel activity.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. jtorres@ntu.edu.sg.

ABSTRACT
Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. Deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows involvement in the regulation of stress and inflammation. The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail. In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains. A deeper analysis of these interactions should not only provide a more complete overview of the multiple functions of these viroporins, but also suggest novel strategies that target protein-protein interactions as much needed antivirals. These should complement current efforts to block viroporin channel activity.

No MeSH data available.


Related in: MedlinePlus

Structural model of RSV SH protein. Top view (a) and side view (b) of the SH protein pentamer [148]. In the latter, one monomer has been removed. The lumenally oriented polar residues (red) and hydrophobic residues (yellow) in the α-helical bundle are indicated.
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viruses-07-02750-f004: Structural model of RSV SH protein. Top view (a) and side view (b) of the SH protein pentamer [148]. In the latter, one monomer has been removed. The lumenally oriented polar residues (red) and hydrophobic residues (yellow) in the α-helical bundle are indicated.

Mentions: The topology of RSV SH protein is just opposite to that of CoV E proteins, with N- and C-terminal extramembrane domains oriented cytoplasmically and lumenally/extracellularly, respectively. The mutual orientation of the transmembrane (TM) α-helices that form the ion channel was determined in lipid bilayers using site specific infrared dichroism [146,147]. A description of the full length SH protein monomer has been obtained by solution NMR in dodecylphosphocholine (DPC) micelles [126] and in bicelles [148]. Like SARS-CoV E, SH protein forms homopentameric channels [126,146] that have low ion selectivity [148]. The TM domain of SH protein has a funnel-like architecture [126] (Figure 4), as observed in other viroporins, e.g., influenza M2 [149], SARS E protein [46] and HCV p7 [150]. A narrower region [126] in the TM domain is lined with hydrophobic side chains (Ile32, Ile36, Ile40 and Leu44) whereas the more open N-terminal region is lined by polar residues, i.e., His22, Thr25 and Ser29 (Figure 4b).


Protein-Protein Interactions of Viroporins in Coronaviruses and Paramyxoviruses: New Targets for Antivirals?

Torres J, Surya W, Li Y, Liu DX - Viruses (2015)

Structural model of RSV SH protein. Top view (a) and side view (b) of the SH protein pentamer [148]. In the latter, one monomer has been removed. The lumenally oriented polar residues (red) and hydrophobic residues (yellow) in the α-helical bundle are indicated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488717&req=5

viruses-07-02750-f004: Structural model of RSV SH protein. Top view (a) and side view (b) of the SH protein pentamer [148]. In the latter, one monomer has been removed. The lumenally oriented polar residues (red) and hydrophobic residues (yellow) in the α-helical bundle are indicated.
Mentions: The topology of RSV SH protein is just opposite to that of CoV E proteins, with N- and C-terminal extramembrane domains oriented cytoplasmically and lumenally/extracellularly, respectively. The mutual orientation of the transmembrane (TM) α-helices that form the ion channel was determined in lipid bilayers using site specific infrared dichroism [146,147]. A description of the full length SH protein monomer has been obtained by solution NMR in dodecylphosphocholine (DPC) micelles [126] and in bicelles [148]. Like SARS-CoV E, SH protein forms homopentameric channels [126,146] that have low ion selectivity [148]. The TM domain of SH protein has a funnel-like architecture [126] (Figure 4), as observed in other viroporins, e.g., influenza M2 [149], SARS E protein [46] and HCV p7 [150]. A narrower region [126] in the TM domain is lined with hydrophobic side chains (Ile32, Ile36, Ile40 and Leu44) whereas the more open N-terminal region is lined by polar residues, i.e., His22, Thr25 and Ser29 (Figure 4b).

Bottom Line: The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail.In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains.These should complement current efforts to block viroporin channel activity.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. jtorres@ntu.edu.sg.

ABSTRACT
Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. Deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows involvement in the regulation of stress and inflammation. The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail. In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains. A deeper analysis of these interactions should not only provide a more complete overview of the multiple functions of these viroporins, but also suggest novel strategies that target protein-protein interactions as much needed antivirals. These should complement current efforts to block viroporin channel activity.

No MeSH data available.


Related in: MedlinePlus