Suppression of human immunodeficiency virus type-1 production by coexpression of catalytic-region-deleted N-myristoyltransferase mutants.
N-Myristoyltransferase (NMT) isozymes, i.e., NMT1 and NMT2, are essential host factors for the AIDS-causing human immunodeficiency virus type-1 (HIV-1), by which the viral proteins Pr55(gag) and Nef are N-myristoylated. N-Myristoylation is important for the membrane targeting of modified proteins. Since it is predicted that approximately 0.5% of all proteins in the human genome are N-myristoylated, selective inhibition of closely HIV-1-associated NMT isozymes is thought to be important for the improvement of specificity in the anti-HIV-1 strategy with the inhibition of NMT function. NMT isozymes contain two characteristic structures, the N-terminal region and the catalytic region. Here, it was shown that the N-terminal region of each NMT isozyme is required for isozyme-specific binding to the ribosome. The specific binding of each isozyme to the ribosome was associated with HIV-1 production, in which NMT1 and NMT2 in the ribosome were suggested to be mainly related to Pr55(gag) and Nef, respectively. These results indicate that the N-terminal region that mediates binding to the ribosome can become a target for NMT-isozyme-specific inhibition, which could block HIV-1 production.
Department of Pharmaceutical Biochemistry, Kumamoto University, Japan. tkmnnbtk@gpo.kumamoto-u-ac.jp
Nobutoki
N
Takamune
Tetsuya
T
Kuroe
Noriaki
N
Tanada
Shozo
S
Shoji
Shogo
S
Misumi
D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D020134:Catalytic Domain / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012270:Ribosomes / Q000378:metabolism*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D014779:Virus Replication
D007527:Isoenzymes; D014764:Viral Proteins; D000217:Acyltransferases