Protein Nef

Function Protein Nef (Nef) or negative regulatory factor is an HIV and SIV accessory protein which establishes a persistent state of infection. Nef downmodulates the surface levels of molecules at the immune synapse. The killer human immunodeficiency virus (HIV) has been contesting with the human immune system for decades. Blunting the epidemic of HIV-induced acquired immuno deficiency syndrome (AIDS) is one of the biggest challenges faced by present day science. The long distressing research effort, thus far, has led to the advent of anti-viral drugs that let the infected people live longer, however, we are yet to find a cure for the infection. The research efforts in the field have undoubtedly revealed some vital facts that make it possible to believe that a breakthrough cure is not far from our reach. One such finding is that of - the role of HIV’s critical protein “Nef” (PDB entry 1qa4, 1qa5). It is one of the most crucial proteins for inducing pathogenesis in host immune system by enhancing viral replication. The absence of Nef sequence from the viral genome renders the virus ineffective by inhibiting its replication. The landmark study by Deacon et al demonstrated that Nef defective virus did not induce AIDS in human population. Nef is a multifunctional accessory protein that is necessary for full HIV-1 virulence. Nef is known to carry out, at least, four genetically separable functions including downregulation of CD4, downregulation of major histocompatibility complex I, activation of p-21 activated protein kinase (Pak2) and enhancement of virion infectivity. Additional Resources For additional information, see: Human Immunodeficiency Virus, HIV and accessory proteins.

spinqualitylabelsall models HIV-I protein Nef (grey) complex with tyrosine protein kinase Hck SH3 domain (green) and ethanediol (PDB code 3rbb) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D Structures of protein Nef3D Structures of protein Nef

Updated on 09-October-2020

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• Protein Nef from HIV; domains – anchor 1-57; core 58-207
  • 3tb8, 2xi1 – Nef – HIV-1
    
  • 1qa5, 1qa4 – Nef anchor domain – NMR
    
  • 1avv, 6b72, 6k6m – Nef core domain
    
  • 2nef – Nef core domain (mutant) – NMR
    
• Protein Nef from HIV complex
  • 4u5w, 3rbb – Nef core domain + tyrosine protein kinase Hck
    
  • 3rea, 3reb – Nef core domain (mutant) + tyrosine protein kinase Hck
    
  • 4d8d, 1avz, 1efn – Nef core domain + tyrosine protein kinase Fyn
    
  • 4orz – Nef core domain + tyrosine protein kinase Hck + single domain antibody
    
  • 4u5w - Nef core domain + tyrosine protein kinase Hck SH3-SH2 domain
    
  • 4nee – Nef core domain + adapter-related protein complex 2 subunits σ, α-2
    
  • 6uri – Nef core domain + adapter-related protein complex 2 subunits σ, α, β, μ + DNA
    
  • 4emz, 4en2 – Nef + adapter-related protein complex 1 subunit μ-1 + MHC-I
    
  • 6d83, 6d84, 6cm9, 6cri – Nef (mutant) + adapter-related protein complex 1 + ARF-1 - Cryo EM
    
  • 6dff – Nef (mutant) + adapter-related protein complex 1 + ARF-1 + GTP - Cryo EM
    
• Protein Nef from SIV
  • 6k6n – Nef core domain
    
  • 3ik5, 3ioz – Nef core domain + CD3 ζ
    
  • 5nuh - Nef core domain + tyrosine protein kinase Hck SH3 domain
    
  • 5nui - Nef core domain + polypeptide