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. 2022

Helena Zábranská, and Aleš Zábranský, and Barbora Lubyová, and Jan Hodek, and Alena Křenková, and Martin Hubálek, and Jan Weber, and Iva Pichová
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.

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.

UI MeSH Term Description Entries
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D002135 Calcium-Binding Proteins Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS. Calcium Binding Protein,Calcium-Binding Protein,Calcium Binding Proteins,Binding Protein, Calcium,Binding Proteins, Calcium,Protein, Calcium Binding,Protein, Calcium-Binding
D003545 Cysteine A thiol-containing non-essential amino acid that is oxidized to form CYSTINE. Cysteine Hydrochloride,Half-Cystine,L-Cysteine,Zinc Cysteinate,Half Cystine,L Cysteine
D004721 Endoplasmic Reticulum A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed) Ergastoplasm,Reticulum, Endoplasmic
D006509 Hepatitis B INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact. Hepatitis B Virus Infection
D006513 Hepatitis B e Antigens A closely related group of antigens found in the plasma only during the infective phase of hepatitis B or in virulent chronic hepatitis B, probably indicating active virus replication; there are three subtypes which may exist in a complex with immunoglobulins G. HBeAg,Hepatitis B e Antigen,Hepatitis Be Antigen,e Antigen,e Antigens,HBe Ag-1,HBe Ag-2,Hepatitis Be Antigens,Antigen, Hepatitis Be,Antigen, e,Antigens, Hepatitis Be,Antigens, e,Be Antigen, Hepatitis,Be Antigens, Hepatitis
D006515 Hepatitis B virus The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum. Dane Particle,Hepatitis Virus, Homologous Serum,B virus, Hepatitis,Hepatitis B viruses,Particle, Dane,viruses, Hepatitis B
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D018000 Receptors, Peptide Cell surface receptors that bind peptide messengers with high affinity and regulate intracellular signals which influence the behavior of cells. Peptide Hormone Receptors,Peptide Receptors,Peptide Hormone Receptor,Peptide Receptor,Receptors, Peptide Hormones,Receptors, Peptides,Hormone Receptor, Peptide,Hormone Receptors, Peptide,Hormones Receptors, Peptide,Peptide Hormones Receptors,Peptides Receptors,Receptor, Peptide,Receptor, Peptide Hormone,Receptors, Peptide Hormone
D018160 Receptors, Cytoplasmic and Nuclear Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS. Cytoplasmic Receptor,Cytoplasmic and Nuclear Receptors,Cytosolic and Nuclear Receptors,Hormone Receptors, Cytoplasmic,Hormone Receptors, Nuclear,Nuclear Hormone Receptor,Nuclear Receptor,Nuclear and Cytoplasmic Receptors,Cytoplasmic Hormone Receptors,Cytoplasmic Receptors,Cytosol and Nuclear Receptors,Intracellular Membrane Receptors,Nuclear Hormone Receptors,Nuclear Receptors,Receptors, Cytoplasmic,Receptors, Cytosol and Nuclear,Receptors, Cytosolic and Nuclear,Receptors, Intracellular Membrane,Receptors, Nuclear,Receptors, Nuclear and Cytoplasmic,Hormone Receptor, Nuclear,Membrane Receptors, Intracellular,Receptor, Cytoplasmic,Receptor, Nuclear,Receptor, Nuclear Hormone,Receptors, Cytoplasmic Hormone,Receptors, Nuclear Hormone

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