Linked Life Data

16867982

Source:http://linkedlifedata.com/resource/pubmed/id/16867982

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2006-9-25
pubmed:abstractText
Hepatitis B virus (HBV) budding from infected cells is a tightly regulated process that requires both core and envelope structures. Here we report that HBV uses cellular gamma2-adaptin and Nedd4, possibly in conjunction with ubiquitin, to coordinate its assembly and release. In search of interaction partners of the viral L envelope protein, we previously discovered gamma2-adaptin, a putative endosomal sorting and trafficking adaptor of the adaptor protein complex family. We now demonstrate that the viral core interacts with the same gamma2-adaptor and that disruption of the HBV/gamma2-adaptin interactions inhibits virus production. Mutational analyses revealed a hitherto unknown ubiquitin-binding activity of gamma2-adaptin, specified by a ubiquitin-interacting motif, which contributes to its interaction with core. For core, the lysine residue at position 96, a potential target for ubiquitination, was identified to be essential for both gamma2-adaptin-recognition and virus production. The participation of the cellular ubiquitin system in HBV assembly was further suggested by our finding that core interacts with the endosomal ubiquitin ligase Nedd4, partly via its late domain-like PPAY sequence. Overexpression of a catalytically inactive Nedd4 mutant diminished HBV egress, indicating that protein ubiquitination is functionally involved in virus production. Additional evidence for a link of HBV assembly to the endosomal machinery was provided by immunolabeling studies that demonstrated colocalization of core and L with gamma2-adaptin in compartments positive for the late endosomal marker CD63. Together, these data indicate that an enveloped DNA virus exploits a new ubiquitin receptor together with endosomal pathway functions for egress from hepatocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29297-308
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16867982-Adaptor Protein Complex gamma Subunits, pubmed-meshheading:16867982-Amino Acid Sequence, pubmed-meshheading:16867982-Antigens, CD, pubmed-meshheading:16867982-Antigens, CD63, pubmed-meshheading:16867982-Catalysis, pubmed-meshheading:16867982-DNA, pubmed-meshheading:16867982-Endosomal Sorting Complexes Required for Transport, pubmed-meshheading:16867982-Hepatitis B virus, pubmed-meshheading:16867982-Humans, pubmed-meshheading:16867982-Lysine, pubmed-meshheading:16867982-Molecular Sequence Data, pubmed-meshheading:16867982-Platelet Membrane Glycoproteins, pubmed-meshheading:16867982-Protein Conformation, pubmed-meshheading:16867982-Sequence Homology, Amino Acid, pubmed-meshheading:16867982-Transfection, pubmed-meshheading:16867982-Ubiquitin, pubmed-meshheading:16867982-Ubiquitin-Protein Ligases
pubmed:year
2006
pubmed:articleTitle
Gamma-adaptin, a novel ubiquitin-interacting adaptor, and Nedd4 ubiquitin ligase control hepatitis B virus maturation.
pubmed:affiliation
Department of Medical Microbiology and Hygiene, Johannes Gutenberg-Universität Mainz, Augustusplatz, D-55101 Mainz, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't