BACTERIAL GLYCOPROTEINS - A LINK BETWEEN GLYCOSYLATION AND PROTEOLYTIC CLEAVAGE OF A 19 KDA ANTIGEN FROM MYCOBACTERIUM-TUBERCULOSIS

Protein glycosylation has an important influence on a broad range of m olecular interactions in eukaryotes, but is comparatively rare in bact eria. Several antigens from Mycobacterium tuberculosis, the causative agent of human tuberculosis, have been identified as glycoproteins on the basis of lectin binding, or by detailed structural analysis. By pr oduction of a set of alkaline phosphatase (PhoA) hybrid proteins in a mycobacterial expression system, the peptide region required for glyco sylation of the 19 kDa lipoprotein antigen from M.tuberculosis was def ined. Mutagenesis of two threonine clusters within this region abolish ed lectin binding by PhoA hybrids and by the 19 kDa protein itself. Su bstitution of the threonine residues also resulted in generation of a series of smaller forms of the protein as a result of proteolysis. In a working model to account for these observations, we propose that the role of glycosylation is to regulate cleavage of a proteolytically se nsitive linker region close to the acylated N-terminus of the protein.