title: 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.
abstract: 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.
authors.affiliation: Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Casartelli
authors.affiliation: Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Giolo
authors.affiliation: Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Neri
authors.affiliation: Department of Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Haller
authors.affiliation: Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Potestà
authors.affiliation: 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.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.affiliation: Department of Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Fackler
authors.affiliation: Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Doria
mesh_terms: 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
chemical_list: D015693:Gene Products, nef; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus; D011392:Proline