Role of the transmembrane domain in severe acute respiratory syndrome (SARS) coronavirus 2 spike for palmitoylation and membrane fusion.

ABSTRACT: Palmitoylation is a reversible post-translational modification that enhances protein hydrophobicity and regulates cellular functions such as trafficking and signaling. In humans, this modification is catalyzed by 23 DHHC enzymes, but the mechanisms by which they recognize their substrates remain unclear. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein undergoes palmitoylation primarily by DHHC20 with subsequent modification by DHHC9 at 10 cytoplasmic tail (CT) cysteines, a modification crucial for membrane fusion and viral entry. Using AlphaFold2 modeling and site-directed mutagenesis, we identified three key components critical for efficient spike palmitoylation: (i) Lys1211 at the ectodomain-transmembrane domain (TMD) interface, likely facilitating electros

SUBMITTER: Abdulrahman DA 

PROVIDER: S-EPMC12828983 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature