The N-terminus of Nef from HIV-1/SIV associates with a protein complex containing Lck and a serine kinase.
The Nef protein of human and primate lentiviruses is a key factor in HIV/SIV pathogenesis. Here we report that Nef associates with two different kinases, forming a multiprotein complex at the far N-terminus of the viral protein. One of the kinases was identified as Lck, whereas the second protein was found to be a serine kinase that phosphorylated Nef and Lck in vitro and could be discriminated from the serine kinase identified previously. The Nef-associated kinase complex (NAKC) was demonstrated in COS cells, in HIV-infected cells, and in vitro using recombinant Lck and Nef proteins. Deletion of a short amphipathic alpha-helix in the N-terminus, which was found to be conserved in all Nef proteins, inhibited association of the NAKC and significantly reduced virion infectivity.
Baur
A S
AS
Institut für Klinische und Molekulare Virologie, Universität Erlangen/Nürnberg, Erlangen, Federal Republic of Germany.
Sass
G
G
Laffert
B
B
Willbold
D
D
Cheng-Mayer
C
C
Peterlin
B M
BM
D000595:Amino Acid Sequence; D015693:Gene Products, nef / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus; D054462:p21-Activated Kinases; D019061:src-Family Kinases / Q000378:metabolism*
D015693:Gene Products, nef; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D009856:Oncogene Proteins, Viral; D054311:nef Gene Products, Human Immunodeficiency Virus; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases