Functional identification of galactosyltransferases (SCGs) required for species-specific modifications of the lipophosphoglycan adhesin controlling Leishmania major-sand fly interactions.
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) (6Galbeta1,4Manalpha1-PO(4)) repeating units. In L. major these are extensively substituted with Gal(beta1,3) 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 beta1,3-galactosyltransferases (betaGalTs). 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 betaGalT 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.
Dobson
Deborah E
DE
Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Scholtes
Luella D
LD
Valdez
Kelli E
KE
Sullivan
Deborah R
DR
Mengeling
Brenda J
BJ
Cilmi
Salvatore
S
Turco
Salvatore J
SJ
Beverley
Stephen M
SM
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D005700:Galactosyltransferases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006028:Glycosphingolipids / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018320:Leishmania major / Q000502:physiology*; D008969:Molecular Sequence Data; D011576:Psychodidae / Q000469:parasitology*; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity
D006028:Glycosphingolipids; D012333:RNA, Messenger; C008290:lipophosphonoglycan; D005700:Galactosyltransferases