Involvement of a putative substrate binding site in the biogenesis and assembly of phosphatidylserine decarboxylase 1 from Saccharomyces cerevisiae
Di Bartolomeo F, Doan KN, Athenstaedt K, Becker T, Daum G.
Mitochondrial membranes are important for the biosynthesis of non-bilayer forming phospholipids. Cardiolipin is synthesized via a multi-step pathway, whereas the phosphatidylserine decarboxylase 1 (Psd1) converts phosphatidylserine into phosphatidylethanolamine (PE). The activity of Psd1 resembles the major source of cellular PE in baker´s yeast Saccharomyces cerevisiae. The biogenesis of Psd1 is a rather complicated process that involves sorting into the inner membrane and processing by two peptidases. Subsequently, Psd1 undergoes an autocatalytic cleavage that is crucial for the activation of the enzyme. Psd1 contains a conserved putative substrate binding site. However, the function of this domain was not shown yet. Here, we reported that mutations within the conserved binding site affect the autocatalytic cleavage of Psd1, which in turn abrogates its enzymatic activity. We identified several residues that are crucial for the autocatalytic maturation and integrity of Psd1. Thus, we conclude that the consensus motif is critical for processing of Psd1.