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Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets
Author(s) -
McLauchlan John,
Lemberg Marius K.,
Hope Graham,
Martoglio Bruno
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf414
Subject(s) - signal peptidase , endoplasmic reticulum , signal peptide , proteolysis , biology , ns3 , microbiology and biotechnology , protein targeting , membrane protein , vesicle associated membrane protein 8 , protease , hepatitis c virus , biochemistry , chemistry , peptide sequence , virus , virology , gene , membrane , enzyme
Hepatitis C virus (HCV) is the major causative pathogen associated with liver cirrhosis and hepatocellular carcinoma. The virus has a positive‐sense RNA genome encoding a single polyprotein with the virion components located in the N‐terminal portion. During biosynthesis of the polyprotein, an internal signal sequence between the core protein and the envelope protein E1 targets the nascent polypeptide to the endoplasmic reticulum (ER) membrane for translocation of E1 into the ER. Following membrane insertion, the signal sequence is cleaved from E1 by signal peptidase. Here we provide evidence that after cleavage by signal peptidase, the signal peptide is further processed by the intramembrane‐cleaving protease SPP that promotes the release of core protein from the ER membrane. Core protein is then free for subsequent trafficking to lipid droplets. This study represents an example of a potential role for intramembrane proteolysis in the maturation of a viral protein.