Allosteric loss-of-function mutations in HIV-1 Nef from a long-term non-progressor.

ABSTRACT: Activation of Src family kinases by human immunodeficiency virus type 1 (HIV-1) Nef may play an important role in the pathogenesis of HIV/AIDS. Here we investigated whether diverse Nef sequences universally activate Hck, a Src family member expressed in macrophages and other HIV-1 target cells. In general, we observed that Hck activation is a highly conserved Nef function. However, we identified an unusual Nef variant from an HIV-positive individual that did not develop AIDS which failed to activate Hck despite the presence of conserved residues linked to Hck SH3 domain binding and kinase activation. Amino acid sequence alignment with active Nef proteins revealed differences in regions not previously implicated in Hck activation, including a large internal flexible loop absent from availab

SUBMITTER: Trible RP 

PROVIDER: S-EPMC2117379 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature