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A family of small activating subunits of serine palmitoyltransferase
Author(s) -
Majumder Saurav,
Han Gongshe,
Gable Kenneth,
Harmon Jeffrey M,
Michaelson Louise V,
Napier Johnathan A,
Dunn Teresa M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.739.9
Serine palmitoyltransferase (SPT) is a multi‐subunit enzyme that catalyzes the first and committed step of sphingolipid biosynthesis. Eukaryotic SPT is composed of two related and highly conserved subunits, LCB1 and LCB2. In yeast, optimal SPT activity requires Tsc3p. Despite the fact that the LCB1‐LCB2 heterodimers from higher eukaryotes have low activity, no Tsc3p homologs exist. This motivated a search for functional orthologs that resulted in the identification of an evolutionarily conserved family of new SPT subunits (ssSPTs). In addition to activating the heterodimers, both Tsc3p and the ssSPTs also affect acyl‐CoA specificity. S. pombe is unusual in that it synthesizes predominantly C20 long‐chain bases (LCBs) compared to the C18 LCBs present in most organisms. This raised questions about the subunit composition of S. pombe SPT. Coexpression of the S. pombe LCB1 and LCB2 subunits in an S. cerevisiae lcb1Δtsc3Δ mutant resulted in much lower microsomal SPT activity than in microsomes from S. pombe , suggesting that there is an activating subunit in S. pombe . Blast searches revealed no Tsc3p homolog, but a very poor ssSPT homolog. Despite its low homology to the ssSPTs, we report that this 101‐amino acid protein is an activating subunit of S. pombe SPT that also activates a broad range of LCB1/LCB2 heterodimers from S. cerevisiae to humans.