RT Journal Article
T1 A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities
A1 Martínez-Bonet, Marta
A1 Palladino, Claudia
A1 Briz, Veronica
A1 Rudolph, Jochen M.
A1 Fackler, Oliver T.
A1 Relloso, Miguel
A1 Muñoz-Fernández, María Ángeles
A1 Madrid González, Ricardo
A2 Yuntao Wu, 
AB To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121–137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection.
PB Public Library of Science
SN 1932-6203
YR 2015
FD 2015
LK https://hdl.handle.net/20.500.14352/97915
UL https://hdl.handle.net/20.500.14352/97915
LA eng
NO Martínez-Bonet M, Palladino C, Briz V, Rudolph JM, Fackler OT, Relloso M, et al. (2015) A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities. PLoS ONE 10(12): e0145239. https://doi.org/10.1371/journal.pone.0145239
NO Comunidad de Madrid
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III
NO German Research Foundation
DS Docta Complutense
RD 4 abr 2025