Document Detail

Role of myristoylation and N-terminal basic residues in membrane association of the human immunodeficiency virus type 1 Nef protein.
MedLine Citation:
PMID:  16476977     Owner:  NLM     Status:  MEDLINE    
Human immunodeficiency virus type 1 Nef protein is N-terminally myristoylated, a modification reported to be required for the association of Nef with cytoplasmic membranes. As myristate alone is not sufficient to anchor a protein stably into a membrane, it has been suggested that N-terminal basic residues contribute to Nef membrane association via electrostatic interactions with acidic phospholipids. Here, data are presented pertaining to the role of the myristate and basic residues in Nef membrane association, subcellular localization and function. Firstly, by using a biochemical assay for membrane association it was shown that, whereas myristoylation of Nef was not essential, mutation of a cluster of four arginines between residues 17 and 22 reduced membrane association dramatically. Mutation of two lysines at residues 4 and 7 had negligible effect alone, but when combined with the arginine substitutions, abrogated membrane association completely. By using indirect immunofluorescence, it was demonstrated that mutation of either of the two basic clusters altered the subcellular distribution of Nef dramatically. Thirdly, the requirement of the arginine and lysine clusters for Nef-mediated CD4 down modulation was shown to correlate precisely with membrane association. These data suggest that membrane localization and subcellular targeting of Nef are controlled by a complex interplay of signals at the N terminus of the protein.
Matthew Bentham; Sabine Mazaleyrat; Mark Harris
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of general virology     Volume:  87     ISSN:  0022-1317     ISO Abbreviation:  J. Gen. Virol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-14     Completed Date:  2006-03-30     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0077340     Medline TA:  J Gen Virol     Country:  England    
Other Details:
Languages:  eng     Pagination:  563-71     Citation Subset:  IM    
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MeSH Terms
Amino Acid Sequence
Antigens, CD4 / metabolism
Arginine / genetics
Cell Membrane / metabolism*
Gene Products, nef / genetics,  metabolism,  physiology*
HeLa Cells
Lysine / genetics
Molecular Sequence Data
Myristic Acid / metabolism*
nef Gene Products, Human Immunodeficiency Virus
Grant Support
G0301041//Medical Research Council
Reg. No./Substance:
0/Antigens, CD4; 0/Gene Products, nef; 0/nef Gene Products, Human Immunodeficiency Virus; 0I3V7S25AW/Myristic Acid; 94ZLA3W45F/Arginine; K3Z4F929H6/Lysine

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