Linked Life Data

16916529

Source:http://linkedlifedata.com/resource/pubmed/id/16916529

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-11-13
pubmed:abstractText
Membrane association is believed to be a prerequisite for the biological activity of the HIV-1 pathogenicity factor Nef. Attachment to cellular membranes as well as incorporation into detergent-insoluble microdomains (lipid rafts) require the N-terminal myristoylation of Nef. However, this modification is not sufficient for sustained membrane association and a specific raft-targeting signal for Nef has not yet been identified. Using live cell confocal microscopy and membrane fractionation analyses, we found that the N-terminal anchor domain (aa 1-61) is necessary and sufficient for efficient membrane binding of Nef from HIV-1(SF2). Within this domain, highly conserved lysine and arginine residues significantly contributed to Nef's membrane association and localization. Plasma membrane localization of Nef was also governed by an additional membrane-targeting motif between residues 40 and 61. Importantly, two lysines at positions 4 and 7 were not essential for the overall membrane association but critically contributed to Nef's incorporation into lipid raft domains. Cell surface receptor downmodulation was largely unaffected by mutations of all N-terminal basic residues, while the association of Nef with Pak2 kinase activity and its ability to augment virion infectivity correlated with its lysine-mediated raft incorporation. In contrast, all basic residues were required for efficient HIV-1 replication in primary human T lymphocytes but did not contribute to the incorporation of Nef into HIV-1 virions. Together, these results unravel that Nef's membrane association is governed by a complex pattern of signature motifs that differentially contribute to individual Nef activities. The identification of a critical raft targeting determinant and the functional characterization of a membrane-bound, non-raft-associated Nef variant indicate raft incorporation as a regulatory mechanism that determines the biological activity of distinct subpopulations of Nef in HIV-infected cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
355
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-91
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16916529-Amino Acid Motifs, pubmed-meshheading:16916529-Artificial Gene Fusion, pubmed-meshheading:16916529-Blotting, Western, pubmed-meshheading:16916529-Cell Fractionation, pubmed-meshheading:16916529-Cell Line, pubmed-meshheading:16916529-Cell Membrane, pubmed-meshheading:16916529-Cells, Cultured, pubmed-meshheading:16916529-Gene Products, nef, pubmed-meshheading:16916529-Green Fluorescent Proteins, pubmed-meshheading:16916529-HIV-1, pubmed-meshheading:16916529-Humans, pubmed-meshheading:16916529-Membrane Microdomains, pubmed-meshheading:16916529-Microscopy, Confocal, pubmed-meshheading:16916529-Microscopy, Fluorescence, pubmed-meshheading:16916529-Protein Binding, pubmed-meshheading:16916529-Protein Sorting Signals, pubmed-meshheading:16916529-Protein Structure, Tertiary, pubmed-meshheading:16916529-Protein-Serine-Threonine Kinases, pubmed-meshheading:16916529-Virus Assembly, pubmed-meshheading:16916529-Virus Replication, pubmed-meshheading:16916529-nef Gene Products, Human Immunodeficiency Virus, pubmed-meshheading:16916529-p21-Activated Kinases
pubmed:year
2006
pubmed:articleTitle
Specific and distinct determinants mediate membrane binding and lipid raft incorporation of HIV-1(SF2) Nef.
pubmed:affiliation
Department of Virology, University of Heidelberg, 69120 Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't