Molecular cloning and characterization of the immunologically protective surface glycoprotein GP46/M-2 of Leishmania amazonensis

Abstract

Immunization of mice with the GP46/M-2 membrane glucoprotein has been demonstrated to elicit protection against infection with the parasitic protozoan Leishmania amazonenis. As this molecule is important for future vaccine studies of leishmaniasis, the gene encoding the GP46/M-2 surface membrane glycoprotein of Leishmania amazonensis has been cloned and sequenced. The protein sequence derived from DNA sequence data is consistent with the known biochemical and immunochemical properties of the protein and indicates a number of structual areas of interest. A repetieive sequence (24 amino acids repeated four times) occurs within the amino-terminal portein. The protease-resistant immunodominant carboxyl-terminal domain of the protein comprises approximately half of the molecule and the protein comprises approximately half of the molecule and consists of proline-rich and cysteine-rich areas of sequence; the distribution of cysteine residues in suggestive of metal binding motifs. The sequence predicts a hydrophobic leader peptide, and a putative attachment site for a glycosyl-phosphatidylinositol anchor is indicated at the carboxyl terminus, consistent with the membrane location of the protein. Southern blot analyses also indicate the presence of a GP46/M-2 gene family.