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Biochim Biophys Acta


Title:An amino terminal prosequence is required for efficient synthesis of S. cerevisiae a-factor
Author(s):Quinby GE; Deschenes RJ;
Address:"Department of Biochemistry, University of Iowa, Iowa City 52242, USA"
Journal Title:Biochim Biophys Acta
Year:1997
Volume:1356
Issue:1
Page Number:23 - 34
DOI: 10.1016/s0167-4889(96)00153-x
ISSN/ISBN:0006-3002 (Print) 0006-3002 (Linking)
Abstract:"The Saccharomyces cerevisiae a-mating pheromones are 12 amino acid lipopeptides whose secretion is dependent on the ABC transporter, Ste6p. The pheromones are synthesized as 36 and 38 amino acid precursors that terminate in a CaaX box (C is Cys, a is an aliphatic residue, and X is the C-terminal amino acid). Posttranslational processing of the a-factor precursors includes at least 5 events. C-terminal processing of the CaaX box includes farnesylation of Cys, removal of the -aaX residues, and methylation of the cysteine alpha-carboxyl group. The N-terminal steps involve proteolytic cleavages that remove the prosequences. In this report, we have investigated the role of posttranslational modification in the generation of functional a-factor. Wild type, mutant and chimeric forms of a-factor have been expressed in yeast and assessed for their abilities to serve as sources of functional a-factor. We have found that although modification of the CaaX box is necessary, it is not sufficient to generate bioactive a-factor. The amino terminal prosequences are also required. Deletion of these sequences reduces intracellular levels of a-factor resulting in sterility. Glutathione-S-transferase (GST)-a-factor fusions undergo CaaX box processing and membrane localization, but are not substrates for the N-terminal proteases and fail to interact with Ste6p. These results suggest that the amino terminal precursor sequences play a direct role in the generation of functional a-factor"
Keywords:"ATP-Binding Cassette Transporters/metabolism Amino Acid Sequence Fungal Proteins/metabolism Gene Expression Glutathione Transferase/metabolism *Glycoproteins Lipoproteins/*biosynthesis/chemistry Methylation Microscopy, Confocal Molecular Sequence Data Phe;"
Notes:"MedlineQuinby, G E Deschenes, R J eng HL42385/HL/NHLBI NIH HHS/ Research Support, U.S. Gov't, P.H.S. Netherlands 1997/03/27 Biochim Biophys Acta. 1997 Mar 27; 1356(1):23-34. doi: 10.1016/s0167-4889(96)00153-x"

 
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