TY - JOUR
T1 - Myristate exchange
T2 - A second glycosyl phosphatidylinositol myristoylation reaction in African trypanosomes
AU - Buxbaum, Laurence U.
AU - Raper, Jayne
AU - Opperdoes, Fred R.
AU - Englund, Paul T.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1994/12/2
Y1 - 1994/12/2
N2 - The variant surface glycoprotein of African trypanosomes has a glycosyl phosphatidylinositol (GPI) anchor that is unusual in that its fatty acids are exclusively myristate. We showed previously that the myristate is added to a free GPI in a fatty acid remodeling reaction involving deacylation and reacylation, forming glycolipid A, the anchor precursor. We now demonstrate that trypanosomes have a second pathway for GPI anchor myristoylation distinct from the fatty acid remodeling pathway, which we call "myristate exchange." This reaction involves exchange of myristate into both the sn-1 and sn-2 positions of glycolipid A, which already contain myristate. Myristoyl-CoA, the probable myristate donor in the exchange reaction, has an apparent Km of about 6 nM. We have now identified a lyso-GPI, named θ′, which has myristate as its sole fatty acid; the kinetics of formation and utilization of θ′ are consistent with it being an intermediate in exchange. Myristate exchange and fatty acid remodeling appear to occur in different subcellular compartments, and the two reactions have different sensitivities to inhibitors. The myristate exchange reaction may be a proofreading system to ensure that the fatty acids on variant surface glycoproteins are exclusively myristate.
AB - The variant surface glycoprotein of African trypanosomes has a glycosyl phosphatidylinositol (GPI) anchor that is unusual in that its fatty acids are exclusively myristate. We showed previously that the myristate is added to a free GPI in a fatty acid remodeling reaction involving deacylation and reacylation, forming glycolipid A, the anchor precursor. We now demonstrate that trypanosomes have a second pathway for GPI anchor myristoylation distinct from the fatty acid remodeling pathway, which we call "myristate exchange." This reaction involves exchange of myristate into both the sn-1 and sn-2 positions of glycolipid A, which already contain myristate. Myristoyl-CoA, the probable myristate donor in the exchange reaction, has an apparent Km of about 6 nM. We have now identified a lyso-GPI, named θ′, which has myristate as its sole fatty acid; the kinetics of formation and utilization of θ′ are consistent with it being an intermediate in exchange. Myristate exchange and fatty acid remodeling appear to occur in different subcellular compartments, and the two reactions have different sensitivities to inhibitors. The myristate exchange reaction may be a proofreading system to ensure that the fatty acids on variant surface glycoproteins are exclusively myristate.
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M3 - Article
C2 - 7982929
AN - SCOPUS:0027987896
SN - 0021-9258
VL - 269
SP - 30212
EP - 30220
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 48
ER -