HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes.
Major-histocompatibility-complex (MHC) proteins are used to display, on the surface of a cell, peptides derived from foreign material - such as a virus - that is infecting that cell. Cytotoxic T lymphocytes then recognize and kill the infected cell. The HIV-1 Nef protein downregulates the cell-surface expression of class I MHC proteins, and probably thereby promotes immune evasion by HIV-1. In the presence of Nef, class I MHC molecules are relocalized from the cell surface to the trans-Golgi network (TGN) through as-yet-unknown mechanisms. Here we show that Nef-induced downregulation of MHC-I expression and MHC-I targeting to the TGN require the binding of Nef to PACS-1, a molecule that controls the TGN localization of the cellular protein furin. This interaction is dependent on Nef's cluster of acidic amino acids. A chimaeric integral membrane protein containing Nef as its cytoplasmic domain localizes to the TGN after internalization, in an acidic-cluster- and PACS-1-dependent manner. These results support a model in which Nef relocalizes MHC-I by acting as a connector between MHC-I's cytoplasmic tail and the PACS-1-dependent protein-sorting pathway.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- nef Gene Products, Human Immunodeficiency Virus
- Vesicular Transport Proteins
- Transfection
- Subtilisins
- Recombinant Fusion Proteins
- Receptor, IGF Type 2
- Rats
- Protein Structure, Tertiary
- Oligonucleotides, Antisense
- Membrane Proteins
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- nef Gene Products, Human Immunodeficiency Virus
- Vesicular Transport Proteins
- Transfection
- Subtilisins
- Recombinant Fusion Proteins
- Receptor, IGF Type 2
- Rats
- Protein Structure, Tertiary
- Oligonucleotides, Antisense
- Membrane Proteins