Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4 - PubMed (original) (raw)

Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4

K Saksela et al. EMBO J. 1995.

Abstract

Human immunodeficiency virus (HIV) and simian immunodeficiency virus Nef proteins contain a conserved motif with the minimal consensus (PxxP) site for Src homology region 3 (SH3)-mediated protein-protein interactions. Nef PxxP motifs show specific binding to biotinylated SH3 domains of Hck and Lyn, but not to those of other tested Src family kinases or less related proteins. A unique cooperative role of a distant proline is also observed. Endogenous Hck of monocytic U937 cells can be specifically precipitated by matrix-bound HIV-1 Nef, but not by mutant protein lacking PxxP. Intact Nef PxxP motifs are dispensable for Nef-induced CD4 down-regulation, but are required for the higher in vitro replicative potential of Nef+ viruses. Thus, CD4 down-regulation and promotion of viral growth are two distinct functions of Nef, and the latter is mediated via SH3 binding.

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References

    1. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):627-31 - PubMed
    1. Virology. 1992 May;188(1):391-5 - PubMed
    1. J Exp Med. 1994 Jan 1;179(1):101-13 - PubMed
    1. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1128-32 - PubMed
    1. J Virol. 1994 May;68(5):3092-101 - PubMed

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