Host-membrane interacting interface of the SARS coronavirus envelope protein: Immense functional potential of C-terminal domain

Abstract

The Envelope (E) protein in SARS Coronavirus (CoV) is a small structural protein, incorporated as part of the envelope. A major fraction of the protein has been known to be associated with the host membranes, particularly organelles related to intracellular trafficking, prompting CoV packaging and propagation. Studies have elucidated the central hydrophobic transmembrane domain of the E protein being responsible for much of the viroporin activity in favor of the virus. However, newer insights into the organizational principles at the membranous compartments within the host cells suggest further complexity of the system. The lesser hydrophobic Carboxylic-terminal of the protein harbors interesting amino acid sequences- suggesting at the prevalence of membrane-directed amyloidogenic properties that remains mostly elusive. These highly conserved segments indicate at several potential membrane-associated functional roles that can redefine our comprehensive understanding of the protein. This should prompt further studies in designing and characterizing of effective targeted therapeutic measures.

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

“…However, this region corresponds to the transmembrane domain. Interestingly, for the envelope (E) protein in SARS-CoV-1, amyloidogenic sequences at the C-terminus were also previously noted [ 258 ]. The same work discusses the possible role of the amyloidogenic sequence in the performance of protein E of its functions of binding to the host cell membranes and formation of ion channels.…”

Environmental Dependence of the Structure of the C-terminal Domain of the SARS-CoV-2 Envelope Protein

“…These changes may occur due to specific inter-molecular interactions of the E-CTD with lipid molecules or salt-bridge interactions, or intra-chain hydrogen bonds [4]. The E-CTD contains the highly conserved cysteine-containing motif CxxC that may allow disulfide isomerization to enhance membrane-directed conformational changes [19].…”

“…In SARS-CoV-2, it has been shown that the envelope protein (E) can promote changes in the properties of lipid membranes of the secretory organelles of the host cells, which help in packaging and releasing the new viral particles [3,4]. E has thus a dual role, since it acts both as a structural protein, being an essential part of the viral capsid, and as a modulator of the cell membrane properties of the host cell during the replication of the virus.…”

“…E has thus a dual role, since it acts both as a structural protein, being an essential part of the viral capsid, and as a modulator of the cell membrane properties of the host cell during the replication of the virus. E is a transmembrane protein with a sequence of 76 amino acids, which has 97% sequence similarity with human SARS-CoV ( Figure 1) and bat SARS-like CoV [4][5][6]. It consists of a hydrophilic N-terminal peptide (E-NTD), a central hydrophobic transmembrane domain (E-TMD) [7], and a weakly hydrophobic C-terminal domain (E-CTD) [8] (Figure 1).…”

Pharmacoinformatics approach based identification of potential Nsp15 endoribonuclease modulators for SARS-CoV-2 inhibition

“…The proteome structure of SARS-CoV-2 consists of four structural proteins, two polyproteins and possibly nine accessory proteins [ 4 ]. The four structural proteins are Spike protein (S), Nucleocapsid protein (N), Membrane protein (M) and Envelope protein (E) which majorly responsible for viral assembly to virion structure constructions and maintaining structural integrity [ 5 ]. Interestingly, these protein sequences are highly similar to the sequences of the corresponding protein of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) [ 6 ].…”