RT Journal Article
SR Electronic
T1 Site-specific lipidation enhances IFITM3 membrane interactions and antiviral activity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.11.293324
DO 10.1101/2020.09.11.293324
A1 Garst, Emma
A1 Lee, Hwayoung
A1 Das, Tandrila
A1 Bhattacharya, Shibani
A1 Percher, Avital
A1 Wiewiora, Rafal
A1 Witte, Isaac P.
A1 Li, Yumeng
A1 Goger, Michael
A1 Peng, Tao
A1 Im, Wonpil
A1 Hang, Howard C.
YR 2020
UL http://biorxiv.org/content/early/2020/09/11/2020.09.11.293324.abstract
AB Interferon-induced transmembrane proteins (IFITMs) are S-palmitoylated proteins in vertebrates that restrict a diverse range of viruses. S-palmitoylated IFITM3 in particular directly engages incoming virus particles, prevents their cytoplasmic entry, and accelerates their lysosomal clearance by host cells. However, the precise molecular mechanisms of action for IFITM-mediated viral restriction are still unclear. To investigate how site-specific S-palmitoylation controls IFITM3 antiviral activity, here we employed computational, chemical, and biophysical approaches to demonstrate that site-specific lipidation of IFITM3 at highly conserved cysteine 72 modulates its conformation and interaction with lipid membranes leading to enhanced antiviral activity of IFITM3 in mammalian cells. Collectively, our results demonstrate that site-specific S-palmitoylation of IFITM3 directly alters its biophysical properties and activity in cells to prevent virus infection.Competing Interest StatementThe authors have declared no competing interest.