The major surface protease (MSP or GP63) of Leishmania sp. Biosynthesis, regulation of expression, and function

• Published in: Molecular & Biochemical Parasitology Vol. 132; no. 1; pp. 1 - 16
• Main Authors: Yao, Chaoqun, Donelson, John E., Wilson, Mary E.
• Format: Book Review Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2003
• Subjects: Amino Acid Sequence; Animals; Biosynthesis; Gene expression; Gene Expression Regulation; GP63; Leishmania; Leishmania - classification; Leishmania - enzymology; Major surface protease; Metalloendopeptidases - biosynthesis; Metalloendopeptidases - chemistry; Metalloendopeptidases - genetics; Molecular Sequence Data; Sequence Alignment; GPI; LPG; T 1/2; GP63; Biosynthesis; MSP; Gene expression; ER; PI-PLC; bp; MAG; Leishmania; kb; Major surface protease; DRM
• ISSN: 0166-6851; 1872-9428
• DOI: 10.1016/S0166-6851(03)00211-1

Leishmania sp. are digenetic protozoa that cause an estimated 1.5–2 million new cases of leishmaniasis per year worldwide. Among the molecular factors that contribute to Leishmania sp. virulence and pathogenesis is the major surface protease, alternately called MSP, GP63, leishmanolysin, EC3.4.24.36, and PSP, which is the most abundant surface protein of leishmania promastigotes. Recent studies using gene knockout, antisense RNA and overexpression mutants have demonstrated a role for MSP in resistance of promastigotes to complement-mediated lysis and either a direct or indirect role in receptor-mediated uptake of leishmania. The MSP gene clusters in different Leishmania sp. include multiple distinct MSPs that tend to fall into three classes, which can be distinguished by their sequences and by their differential expression in parasite life stages. Regulated expression of MSP class gene products during the parasite life cycle occurs at several levels involving both mRNA and protein metabolism. In this review we summarize advances in MSP research over the past decade, including organization of the gene families, crystal structure of the protein, regulation of mRNA and protein expression, biosynthesis and possible functions. The MSPs exquisitely demonstrate the multiple levels of post-transcriptional gene regulation that occur in Leishmania sp. and other trypanosomatid protozoa.