Membrane binding proteins of coronaviruses

J Alsaadi, Entedar A; Jones, Ian M

The endodomain of S2 can been subdivided into two regions, a cysteine-rich region at the N-terminus and a carboxy-terminal region rich in charged residues [31] [32] [33] . It has been shown that clusters of cysteine residues are important for the palmitoylation of S. No particular cysteine residue is critical but in a study of fusion competence and replication in MHV a total of at least three cysteine residues was required [34] and other studies have confirmed that the cysteine-rich region is necessary for syncytium formation during viral infection [35, 36] . While membrane binding and deformation is clearly a property of the FP sequence, propelled into the membrane by the conformational changes in S, palmitoylation of S may serve to stabilize the protein during its interactions with lipid rafts in the target membranes to allow time for fusion to occur. Recently, several CoV-S proteins including HCoV-HKU1, MHV, HCoV-NL63, SARS-CoV and MERS-CoV have had their structures solved at atomic resolution following imaging using cryo-electron microscopy [37] [38] [39] [40] . All the confirmed structures of S are in their prefusion state and most have had their cleavage sites mutated to enhance S stability in order to enable the imaging process. As a result there is limited knowledge of the CoV FP within the fusion active conformation or of its structural characteristics when interacting with lipid bilayers after proteolytic processing at the S2`site [30, 38, 40] .