Nonidentical subunits of p21(H-ras) farnesyltransferase. Peptide binding and farnesyl pyrophosphate carrier functions

Y. Reiss, M. C. Seabra, S. A. Armstrong, C. A. Slaughter, J. L. Goldstein, M. S. Brown

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Abstract

The protein farnesyltransferase purified from rat brain contains two nonidentical subunits, α and β. The holoenzyme forms a stable complex with [3H]farnesyl pyrophosphate (FPP) that can be isolated by gel filtration. The [3H]FPP is not covalently bound to the enzyme; it is released unaltered when the enzyme is denatured. When incubated with an acceptor such as p21(H-ras), the complex transfers [3H]farnesyl from the bound [3H]FPP to the ras protein. This transfer is not sensitive to dilution by unbound FPP, suggesting that the [3H]FPP is bound at a site that leads to direct transfer to the p21(H-ras) acceptor. Cross-linking studies show that the p21(H-ras) binds to the lower molecular weight subunit (β-subunit), raising the possibility that the [3H]FPP binds to the α-subunit. If this suggestion can be confirmed, it would invoke a reaction mechanism in which the α-subunit acts as a prenyl pyrophosphate carrier that delivers FPP to p21(H-ras) which is bound to the β-subunit.

Original languageEnglish (US)
Pages (from-to)10672-10677
Number of pages6
JournalJournal of Biological Chemistry
Volume266
Issue number16
Publication statusPublished - Aug 16 1991
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Reiss, Y., Seabra, M. C., Armstrong, S. A., Slaughter, C. A., Goldstein, J. L., & Brown, M. S. (1991). Nonidentical subunits of p21(H-ras) farnesyltransferase. Peptide binding and farnesyl pyrophosphate carrier functions. Journal of Biological Chemistry, 266(16), 10672-10677.