A-Factor: A chemical biology tool for the study of protein prenylation

Veronica Diaz-Rodriguez, Mark D Distefano

Research output: Contribution to journalReview article

3 Scopus citations

Abstract

The mating pheromone a-factor is a lipidated dodecapeptide found in the budding yeast S. cerevisiae. The biosynthesis of this peptide encompasses the same three-step processing pathway (farnesylation of C-terminal cysteine, C-terminal proteolysis and C-terminal methyl esterification) as Ras proteins, mutated forms of which have been found in ∼30% of human cancers. For the mating of two haploid yeast cells into a diploid cell to happen, the a-factor pheromone travels to the cell surface of the opposite mating cell, where it binds to and activates a G-protein coupled receptor (GPCR). This lipidated-peptide/protein interaction has caught the attention of researchers studying protein prenylation, and studies have shown that this peptide can be used as a model system to understand the role of prenyl groups in protein-protein interactions. Here, we review the different methods used for the synthesis of a-factor and a-factor analogs containing C-terminal cysteine esters and the assays developed for detecting pheromone bioactivity and quantitation of pheromone efficiency. Also, we review crucial peptide modifications that have been used to investigate relationships between the structure and activity of this lipopeptide with its receptor Ste3p. Finally, we aim to discuss recent and future applications of a-factor as a chemical biology tool to study protein prenylation. These include the use of photo crosslinking reactions to map peptide/receptor interactions, the addition of fluorophore tags to visualize the peptide binding, and the use of bio-orthogonal reactions for protein labeling and protein purification.

Original languageEnglish (US)
Pages (from-to)133-151
Number of pages19
JournalCurrent Topics in Peptide and Protein Research
Volume18
StatePublished - Jan 1 2017

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Keywords

  • A-factor
  • Farnesylation
  • Farnesyltransferase
  • Isoprenoid
  • Protein prenylation
  • Rce1
  • Ste24

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