RT Journal Article
T1 HIV-1 Nef Stabilizes the Association of Adaptor Protein Complexes with Membranes
A1 Janvier, Katy
A1 Craig, Heather
A1 Hitchin, Douglas
A1 Madrid González, Ricardo
A1 Sol-Foulon, Nathalie
A1 Renault, Louis
A1 Cherfils, Jacqueline
A1 Cassel, Dan
A1 Benichou, Serge
A1 Guatelli, John
AB The maximal virulence of HIV-1 requires Nef, a virally encoded peripheral membrane protein. Nef binds to the adaptor protein (AP) complexes of coated vesicles, inducing an expansion of the endosomal compartment and altering the surface expression of cellular proteins including CD4 and class I major histocompatibility complex. Here, we show that Nef stabilizes the association of AP-1 and AP-3 with membranes. These complexes remained with Nef on juxtanuclear membranes despite the treatment of cells with brefeldin A, which induced the release of ADP-ribosylation factor 1 (ARF1) from these membranes to the cytosol. Nef also induced a persistent association of AP-1 and AP-3 with membranes despite the expression of dominant-negative ARF1 or the overexpression of an ARF1-GTPase activating protein. Mutational analysis indicated that the direct binding of Nef to the AP complexes is essential for this stabilization.The leucine residues of the EXXXLL motif found in Nef were required for binding to AP-1 and AP-3 in vitro and for the stabilization of these complexes on membranes in vivo, whereas the glutamic acid residue of this motif was required specifically for the binding and stabilization of AP-3. These data indicate that Nef mediates the persistent attachment of AP-1 and AP-3 to membranes by an ARF1-independent mechanism. The stabilization of these complexes on membranes may underlie the pleiotropic effects of Nef on protein trafficking within the endosomal system.
SN 0021-9258
YR 2003
FD 2003
LK https://hdl.handle.net/20.500.14352/98116
UL https://hdl.handle.net/20.500.14352/98116
LA eng
NO Janvier, Katy, et al. «HIV-1 Nef Stabilizes the Association of Adaptor Protein Complexes with Membranes». Journal of Biological Chemistry, vol. 278, n.o 10, marzo de 2003, pp. 8725-32. https://doi.org/10.1074/jbc.M210115200.
DS Docta Complutense
RD 11 abr 2025