Linked Life Data

21762808

Source:http://linkedlifedata.com/resource/pubmed/id/21762808

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-7-18
pubmed:abstractText
The characteristic event that follows infection of a cell by retroviruses Including human immunodeficiency virus (HIV)/ simian immunodeficiency virus (SIV) is the formation of a reverse transcription complex in which viral nucleic acids are synthesized. Nuclear transport of newly synthesized viral DNA requires phosphorylation of proteins in the reverse transcription complex by virion-associated cellular kinases. Recently, we demonstrated that disruption of cellular mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 2 (ERK-2) incorporation into SIV virions inhibits virus replication in nonproliferating target cells, indicating that MAPK/ERK-2 plays an important role in HIV /SIV replication. The mechanism of incorporation of MAPK/ERK-2 into virus particles is not defined. In this regard, we hypothesized that a likely interaction of MAPK/ERK-2 with Gag(p55) may enable its packaging into virus particles. In the present investigation, we provided evidence for the first time that MAPK/ERK-2 interacts with the structural Gag polyprotein p55 using a combination of mutagenesis and protein-protein interaction analysis. We further show that MAPK/ERK-2 interacts specifically with the poly-proline motif present in the capsid region of Gag(p55). Utilizing virus-like particles directed by Gag, we have shown that the exchange of conserved proline residues within capsid of Gag(p55) resulted in impaired incorporation of MAPK/ERK-2. In addition, the deletion of a domain comprising amino acids 201 to 255 within host cell MAPK/ERK-2 abrogates its interaction with Gag(p55). The relevance of the poly-proline motif is further evident by its conservation in diverse retroviruses, as noted from the sequence analysis and structural modeling studies of predicted amino acid sequences of the corresponding Gag proteins. Collectively, these data suggest that the interaction of MAPK/ERK-2 with Gag polyprotein results in its incorporation into virus particles and may be essential for retroviral replication.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
410
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
681-97
pubmed:meshHeading
pubmed-meshheading:21762808-Amino Acid Sequence, pubmed-meshheading:21762808-Capsid, pubmed-meshheading:21762808-Conserved Sequence, pubmed-meshheading:21762808-DNA Replication, pubmed-meshheading:21762808-Gene Products, gag, pubmed-meshheading:21762808-HIV-1, pubmed-meshheading:21762808-HeLa Cells, pubmed-meshheading:21762808-Humans, pubmed-meshheading:21762808-Lentivirus, pubmed-meshheading:21762808-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:21762808-Molecular Sequence Data, pubmed-meshheading:21762808-Mutation, pubmed-meshheading:21762808-Proline-Rich Protein Domains, pubmed-meshheading:21762808-Protein Binding, pubmed-meshheading:21762808-Simian immunodeficiency virus, pubmed-meshheading:21762808-Structure-Activity Relationship, pubmed-meshheading:21762808-Virion, pubmed-meshheading:21762808-Virus Assembly
pubmed:year
2011
pubmed:articleTitle
Mechanism of host cell MAPK/ERK-2 incorporation into lentivirus particles: characterization of the interaction between MAPK/ERK-2 and proline-rich-domain containing capsid region of structural protein Gag.
pubmed:affiliation
Laboratory of Molecular Virology and Cell Biology, Department of Biotechnology, Indian Institute of Technology-Madras, Chennai, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't