The Pro78 residue regulates the capacity of the human immunodeficiency virus type 1 Nef protein to inhibit recycling of major histocompatibility complex class I molecules in an SH3-independent manner.
The Nef protein is a crucial pathogenicity factor of human immunodeficiency virus type 1 (HIV-1) that contains a proline-rich motif consisting of four conserved prolines: Pro69 (P69), P72, P75 and P78. P72 and P75 were shown to bind Src homology domains 3 (SH3) and have been implicated in many biological functions of Nef, including downmodulation of cell-surface major histocompatibility complex class I (MHC-I). P78 is involved together with P69 in positioning of the Nef-SH3 complex and it has been shown to be essential for Nef activity of MHC-I downmodulation. It is shown here that alteration of P78 affects recycling of MHC-I molecules to the cell surface, but does not interfere with SH3 binding. In addition, it is demonstrated that P72 and P75, and thus the SH3-binding capacity, are fully dispensable for Nef activity on MHC-I.
Casartelli
Nicoletta
N
Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
Giolo
Giorgia
G
Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
Neri
Francesca
F
Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
Haller
Claudia
C
Department of Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany.
Potestà
Marina
M
Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
Rossi
Paolo
P
Department of Pediatrics, University Tor Vergata, 00133 Rome, Italy.|Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
Fackler
Oliver T
OT
Department of Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany.
Doria
Margherita
M
Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
D019943:Amino Acid Substitution; D005434:Flow Cytometry; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015497:HIV-1; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D009154:Mutation; D011392:Proline / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D054311:nef Gene Products, Human Immunodeficiency Virus; D018909:src Homology Domains
D015693:Gene Products, nef; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus; D011392:Proline