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Biogenesis of hepatitis B virus e antigen is driven by translocon‐associated protein complex and regulated by conserved cysteine residues within its signal peptide sequence
Author(s) -
Zábranská Helena,
Zábranský Aleš,
Lubyová Barbora,
Hodek Jan,
Křenková Alena,
Hubálek Martin,
Weber Jan,
Pichová Iva
Publication year - 2022
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.16304
Subject(s) - signal peptide , endoplasmic reticulum , translocon , biogenesis , biology , cytoplasm , cleavage (geology) , microbiology and biotechnology , peptide sequence , signal peptidase , cysteine , virus , virology , biochemistry , chromosomal translocation , paleontology , fracture (geology) , gene , enzyme
Hepatitis B virus uses e antigen (HBe), which is dispensable for virus infectivity, to modulate host immune responses and achieve viral persistence in human hepatocytes. The HBe precursor (p25) is directed to the endoplasmic reticulum (ER), where cleavage of the signal peptide (sp) gives rise to the first processing product, p22. P22 can be retro‐translocated back to the cytosol or enter the secretory pathway and undergo a second cleavage event, resulting in secreted p17 (HBe). Here, we report that translocation of p25 to the ER is promoted by translocon‐associated protein complex. We have found that p25 is not completely translocated into the ER; a fraction of p25 is phosphorylated and remains in the cytoplasm and nucleus. Within the p25 sp sequence, we have identified three cysteine residues that control the efficiency of sp cleavage and contribute to proper subcellular distribution of the precore pool.