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. 2022 May:570:1-8.
doi: 10.1016/j.virol.2022.03.002. Epub 2022 Mar 15.

Unique properties of Coronaviridae single-pass transmembrane domain regions as an adaptation to diverse membrane systems

Szymon Kubiszewski-Jakubiak  1 , Remigiusz Worch  2
Affiliations

Unique properties of Coronaviridae single-pass transmembrane domain regions as an adaptation to diverse membrane systems

Szymon Kubiszewski-Jakubiak et al. Virology. 2022 May.

Abstract

Enveloped viruses such as Coronaviridae (CoV) enter the host cell by fusing the viral envelope directly with the plasma membrane (PM) or with the membrane of the endosome. Replication of the CoV genome takes place in membrane compartments formed by rearrangement of the endoplasmic reticulum (ER) membrane network. Budding of these viruses occurs from the ER-Golgi intermediate compartment (ERGIC). The relationship between proteins and various membranes is crucial for the replication cycle of CoVs. The role of transmembrane domains (TMDs) and pre-transmembrane domains (pre-TMD) of viral proteins in this process is gaining more recognition. Here we present a thorough analysis of physico-chemical parameters, such as accessible surface area (ASA), average hydrophobicity (Hav), and contribution of specific amino acids in TMDs and pre-TMDs of single-span membrane proteins of human viruses. We focus on unique properties of these elements in CoV and postulate their role in adaptation to diverse host membranes and regulation of retention of membrane proteins during replication.

Keywords: Accessible surface area (ASA); Average hydrophobicity (H(av)); Lipid rafts; Retention; Trafficking.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Coronaviridae (CoV) TMD have larger (a) ASA and (b) are more hydrophobic as compared to other viruses. Corresponding values for TMDs of human membrane proteins in ER, Golgi and plasma membrane (PM) are shown in the lower panel. The values for Coronaviridae differ significantly from all others: (Wilcoxon test) p-values < 0.001 in all cases, except for Coronaviridae and Golgi ASA (p < 0.02).
Fig. 2
Fig. 2
Coronaviridae (CoV) TMD have fewer (a) polar, (b) strongly polar and (c) charged amino acids as compared to other viruses. Corresponding values for human TMDs of human membrane proteins in ER, Golgi and plasma membrane (PM) are shown in the lower panel. The values for Coronaviridae differ significantly from all others: (Wilcoxon test) p-values < 0.001 in all cases, except for the numbers of charged amino acids in Coronaviridae and plasma membrane proteins (p = 0.56).
Fig. 3
Fig. 3
Wenxiang diagrams for the (a) wild-type SARS-CoV ORF7b TMD and two mutations exhibiting impaired retention in Golgi (b) and (c), respectively. Color code: F and W: magenta, I: green, L: yellow, V: red, other: grey. Mutated residues marked with an asterisk. Sizes of the amino acids are proportional to ASA. Hav and ASA calculated for the most hydrophobic 19 amino acid fragment (see Materials and Methods for details).
Fig. 4
Fig. 4
Physico-chemical parameters for TMDs of viruses budding by cellular exocytosis. (a) ASA of TMDs is larger for viruses budding by exocytosis (Wilcoxon test, p-value <0.05), (b) Coronaviridae and Flaviviridae appear in clusters on Hav vs ASA map in contrast to Herpesviridae and Poxviridae (c).
Fig. 5
Fig. 5
Coronaviridae (CoV) pre-TMD regions are enriched in aromatic residues as compared to other viruses. The panels show (a) all aromatic residues, (b) W, (c) Y and (d) F. p-values (Wilcoxon test): (a) p < 0.05, (b) and (c) p < 0.001, (d) p < 0.08.
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