TY - JOUR
T1 - Functional identification of galactosyltransferases (SCGs) required for species-specific modifications of the lipophosphoglycan adhesin controlling Leishmania major-sand fly interactions
AU - Dobson, Deborah E.
AU - Scholtes, Luella D.
AU - Valdez, Kelli E.
AU - Sullivan, Deborah R.
AU - Mengeling, Brenda J.
AU - Cilmi, Salvatore
AU - Turco, Salvatore J.
AU - Beverley, Stephen M.
PY - 2003/5/2
Y1 - 2003/5/2
N2 - Lipophosphoglycan (LPG) is an abundant surface molecule that plays key roles in the infectious cycle of Leishmania major. The dominant feature of LPG is a polymer of phosphoglycan (PG) (6Galβ1,4Manα1-PO4) repeating units. In L. major these are extensively substituted with Gal(β1,3) side chains, which are required for binding to midgut lectins and survival. We utilized evolutionary polymorphisms in LPG structure and cross-species transfections to recover genes encoding the LPG side chain β1,3-galactosyltransferases (βGalTs). A dispersed family of six SCG genes was recovered, whose predicted proteins exhibited characteristics of eukaryotic GalTs. At least four of these proteins showed significant LPG side chain βGalT activity; SCG3 exhibited initiating GalT activity whereas SCG2 showed both initiating and elongating GalT activity. However, the activity of SCG2 was context-dependent, being largely silent in its normal genomic milieu, and different strains show considerable variation in the extent of LPG galactosylation. Thus the L. major genome encodes a family of SCGs with varying specificity and activity, and we propose that strain-specific LPG galactosylation patterns reflect differences in their expression.
AB - Lipophosphoglycan (LPG) is an abundant surface molecule that plays key roles in the infectious cycle of Leishmania major. The dominant feature of LPG is a polymer of phosphoglycan (PG) (6Galβ1,4Manα1-PO4) repeating units. In L. major these are extensively substituted with Gal(β1,3) side chains, which are required for binding to midgut lectins and survival. We utilized evolutionary polymorphisms in LPG structure and cross-species transfections to recover genes encoding the LPG side chain β1,3-galactosyltransferases (βGalTs). A dispersed family of six SCG genes was recovered, whose predicted proteins exhibited characteristics of eukaryotic GalTs. At least four of these proteins showed significant LPG side chain βGalT activity; SCG3 exhibited initiating GalT activity whereas SCG2 showed both initiating and elongating GalT activity. However, the activity of SCG2 was context-dependent, being largely silent in its normal genomic milieu, and different strains show considerable variation in the extent of LPG galactosylation. Thus the L. major genome encodes a family of SCGs with varying specificity and activity, and we propose that strain-specific LPG galactosylation patterns reflect differences in their expression.
UR - http://www.scopus.com/inward/record.url?scp=0038121032&partnerID=8YFLogxK
U2 - 10.1074/jbc.M301568200
DO - 10.1074/jbc.M301568200
M3 - Article
C2 - 12604613
AN - SCOPUS:0038121032
VL - 278
SP - 15523
EP - 15531
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 18
ER -