TY - JOUR
T1 - Fatty acid remodeling of glycosyl phosphatidylinositol anchors in Trypanosoma brucei
T2 - Incorporation of fatty acids other than myristate
AU - Morita, Yasu S.
AU - Englund, Paul T.
N1 - Funding Information:
We thank Alvaro Acosta-Serrano, David Jiang, and Kimberly Paul for discussions and critical reading of the manuscript, Viiu Klein for her valuable assistance, and our lab colleagues for their encouragement. This research was supported by NIH (grant AI21334).
PY - 2001/7
Y1 - 2001/7
N2 - Trypanosoma brucei is the protozoan parasite that causes African sleeping sickness. Its surface is packed with 107 copies of the glycosyl phosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). This GPI anchor is unusual in that it contains two myristates (14:0) in its lipid moiety. This fatty acid specificity is achieved through myristoylation of the GPI precursor, and the acyltransferases involved in the GPI remodeling were presumed to be specific for myristate. However, their specificity had never been fully evaluated. Here we found as expected that the remodeling acyltransferases completely excluded palmitate (16:0) and stearate (18:0) in a cell-free fatty acid remodeling system. In contrast, we found surprisingly that one of these enzymes was permissive to shorter fatty acids such as laurate (12:0) and octanoate (8:0). However, the rates of incorporation of shorter fatty acids were lower than that of myristate at low substrate concentration. Since shorter fatty acids are virtually absent in the parasite and in the host bloodstream, it is unlikely that shorter fatty acids compete effectively with myristate as remodeling substrates under physiological conditions. Even if they were present in small quantities, a recently identified specialized fatty acid synthetase efficiently elongates shorter fatty acids to myristate prior to incorporation into GPIs (Morita et al., Science 288 (2000) 140-3.). Therefore, even though a remodeling acyltransferase is permissive with regard to substrate chain length, the myristate specificity in GPI anchors is very high.
AB - Trypanosoma brucei is the protozoan parasite that causes African sleeping sickness. Its surface is packed with 107 copies of the glycosyl phosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). This GPI anchor is unusual in that it contains two myristates (14:0) in its lipid moiety. This fatty acid specificity is achieved through myristoylation of the GPI precursor, and the acyltransferases involved in the GPI remodeling were presumed to be specific for myristate. However, their specificity had never been fully evaluated. Here we found as expected that the remodeling acyltransferases completely excluded palmitate (16:0) and stearate (18:0) in a cell-free fatty acid remodeling system. In contrast, we found surprisingly that one of these enzymes was permissive to shorter fatty acids such as laurate (12:0) and octanoate (8:0). However, the rates of incorporation of shorter fatty acids were lower than that of myristate at low substrate concentration. Since shorter fatty acids are virtually absent in the parasite and in the host bloodstream, it is unlikely that shorter fatty acids compete effectively with myristate as remodeling substrates under physiological conditions. Even if they were present in small quantities, a recently identified specialized fatty acid synthetase efficiently elongates shorter fatty acids to myristate prior to incorporation into GPIs (Morita et al., Science 288 (2000) 140-3.). Therefore, even though a remodeling acyltransferase is permissive with regard to substrate chain length, the myristate specificity in GPI anchors is very high.
KW - Fatty acid remodeling
KW - Glycosyl phosphatidylinositol
KW - Myristate
KW - Trypanosoma brucei
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U2 - 10.1016/S0166-6851(01)00279-1
DO - 10.1016/S0166-6851(01)00279-1
M3 - Article
C2 - 11420102
AN - SCOPUS:0035400391
VL - 115
SP - 157
EP - 164
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
SN - 0166-6851
IS - 2
ER -