A NOVEL ACYL-COA THIOESTERASE ENHANCES ITS ENZYMATIC-ACTIVITY BY DIRECT BINDING WITH HIV NEF

In addition to playing a crucial role in the pathogenesis of AIDS, HIV nef induces down-regulation of CD4 expression and TCR signaling and a lso regulates the sorting pathway in host T cells. To elucidate the Ne f function in HIV progression, me searched for a cellular component wh ich interacts with Nef. A human cDNA encoding a novel acyl-CoA thioest erase (hACTE-III) was isolated as an HN nef-binding protein by yeast t wo-hybrid system. hACTE-III is homologous to E. coli thioesterase II b ut to none of the mammalian thioesterases and therefore belongs to a n ew type. hACTE-III exhibits enzymatic specificity fop a broad range of fatty acyl-CoAs. The hACTE-III-binding region within Nef is localized in the central region (amino acids 109-152), hACTE-III greatly enhanc es its enzymatic activity upon direct binding to Nef. Considering that either Nef-overexpression or impaired fatty acid regulation induces a lteration of subcellular morphology, the augmented hACTE-III function by Nef-binding might induce dysfunction of T cells. (C) 1997 Academic Press.