PXD025430

PXD025430 is an original dataset announced via ProteomeXchange.

Title	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
Description	Hepatitis B virus (HBV) uses e antigen (HBe) which is dispensable for virus infectivity to modulate host immune responses and to 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. The p22 can be retro-translocated back to the cytosol or it can enter the secretory pathway and undergo a second cleavage event resulting in secreted p17 (HBe). Here, we report that translocation of p25 precursor is promoted by translocon-associated protein complex (TRAP). We found that p25 is not completely translocated into the ER since a fraction of p25 is phosphorylated and remains present in the cytoplasm and the nucleus. Within the sp sequence of p25 we identified three cysteine residues which control the efficiency of sp cleavage and correct subcellular distribution of the precore pool. Highlights • A fraction of the HBV e antigen precursor p25 is not translocated into the ER and is phosphorylated in cytosol. • Cysteine residues in the signal peptide sequence regulate the p25 N-terminal processing and resulting p22 intracellular level. • Mutations of all three Cys residues within the signal peptide lead to a mislocalization of intracellular precore protein. • P25 translocation requires assistance of TRAP complex for an efficient mature HBe secretion. • The depletion of individual TRAP subunits results in a change of precore subcellular distribution.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:18.419.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD025430
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Martin Hubalek
SpeciesList	scientific name: Hepatitis B virus; NCBI TaxID: 10407; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine; phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-15 22:25:26	ID requested
1	2022-07-01 06:41:56	announced
⏵ 2	2023-11-14 08:52:18	announced	2023-11-14: Updated project metadata.

10.6019/PXD025430;

submitter keyword: HBe, ER translocation,Hepatitis B virus, HBV precore protein, TRAP complex, signal peptide, cysteine residues

Martin Hubálek
contact affiliation	Institute of organic chemistry and biochemistry, CAS, Prague, Czech republic
contact email	hubalek@uochb.cas.cz
lab head
Martin Hubalek
contact affiliation	Institute of Organic Chemistry and Biochemistry, Czech Academy of Science
contact email	hubalek@uochb.cas.cz
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025430
     1. Label: PRIDE project
     2. Name: 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