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.
Similar articles
- A single amino acid in the SH3 domain of Hck determines its high affinity and specificity in binding to HIV-1 Nef protein.
Lee CH, Leung B, Lemmon MA, Zheng J, Cowburn D, Kuriyan J, Saksela K. Lee CH, et al. EMBO J. 1995 Oct 16;14(20):5006-15. doi: 10.1002/j.1460-2075.1995.tb00183.x. EMBO J. 1995. PMID: 7588629 Free PMC article. - The cellular kinase binding motifs (PxxP and RR) in human immunodeficiency virus type 1 Nef protein are dispensable for producer-cell-dependent enhancement of viral entry.
Tokunaga K, Ikuta K, Adachi A, Matsuda M, Kurata T, Kojima A. Tokunaga K, et al. Virology. 1999 May 10;257(2):285-9. doi: 10.1006/viro.1999.9682. Virology. 1999. PMID: 10329538 - Simian immunodeficiency virus and human immunodeficiency virus type 1 nef proteins show distinct patterns and mechanisms of Src kinase activation.
Greenway AL, Dutartre H, Allen K, McPhee DA, Olive D, Collette Y. Greenway AL, et al. J Virol. 1999 Jul;73(7):6152-8. doi: 10.1128/JVI.73.7.6152-6158.1999. J Virol. 1999. PMID: 10364375 Free PMC article. - Reading between the lines: SH3 recognition of an intact protein.
Lim WA. Lim WA. Structure. 1996 Jun 15;4(6):657-9. doi: 10.1016/s0969-2126(96)00071-8. Structure. 1996. PMID: 8805558 Review. - Use of the two-hybrid system to identify cellular partners of the HIV1 Nef protein.
Benichou S, Liu LX, Erdtmann L, Selig L, Benarous R. Benichou S, et al. Res Virol. 1997 Jan-Feb;148(1):71-3. doi: 10.1016/s0923-2516(97)81918-8. Res Virol. 1997. PMID: 9017839 Review. No abstract available.
Cited by
- Prediction of virus-host interactions and identification of hot spot residues of DENV-2 and SH3 domain interactions.
Banik M, Paudel KR, Majumder R, Idrees S. Banik M, et al. Arch Microbiol. 2024 Mar 14;206(4):162. doi: 10.1007/s00203-024-03892-x. Arch Microbiol. 2024. PMID: 38483579 Free PMC article. - Kinetic investigation reveals an HIV-1 Nef-dependent increase in AP-2 recruitment and productivity at endocytic sites.
Iwamoto Y, Ye AA, Shirazinejad C, Hurley JH, Drubin DG. Iwamoto Y, et al. Mol Biol Cell. 2024 Jan 1;35(1):ar9. doi: 10.1091/mbc.E23-04-0126. Epub 2023 Nov 8. Mol Biol Cell. 2024. PMID: 37938925 Free PMC article. - Interaction with the carboxy-terminal tip of SSB is critical for RecG function in E. coli.
Bonde NJ, Henry C, Wood EA, Cox MM, Keck JL. Bonde NJ, et al. Nucleic Acids Res. 2023 May 8;51(8):3735-3753. doi: 10.1093/nar/gkad162. Nucleic Acids Res. 2023. PMID: 36912097 Free PMC article. - AP-2 Adaptor Complex-Dependent Enhancement of HIV-1 Replication by Nef in the Absence of the Nef/AP-2 Targets SERINC5 and CD4.
Olety B, Usami Y, Wu Y, Peters P, Göttlinger H. Olety B, et al. mBio. 2023 Feb 28;14(1):e0338222. doi: 10.1128/mbio.03382-22. Epub 2023 Jan 9. mBio. 2023. PMID: 36622146 Free PMC article. - Apoptosis regulation by the tyrosine-protein kinase CSK.
Fortner A, Chera A, Tanca A, Bucur O. Fortner A, et al. Front Cell Dev Biol. 2022 Dec 12;10:1078180. doi: 10.3389/fcell.2022.1078180. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 36578781 Free PMC article. Review.
References
- Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):627-31 - PubMed
- Virology. 1992 May;188(1):391-5 - PubMed
- J Exp Med. 1994 Jan 1;179(1):101-13 - PubMed
- Proc Natl Acad Sci U S A. 1989 Feb;86(4):1128-32 - PubMed
- J Virol. 1994 May;68(5):3092-101 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous