Document Detail

Myristate exchange in glycolipid A and VSG of African trypanosomes.
MedLine Citation:
PMID:  8081218     Owner:  NLM     Status:  MEDLINE    
The variant surface glycoprotein (VSG) of T. brucei is anchored to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor which is unique in that its fatty acids are exclusively myristate (a fourteen carbon saturated fatty acid). We showed that the myristate is added to the GPI precursor in a remodeling reaction involving deacylation and reacylation. We now demonstrate that trypanosomes have a second pathway of myristoylation for GPI anchors that we call "myristate exchange" which is distinct from the fatty acid remodeling pathway. We propose that this is an exchange of [3H]myristate into both sn-1 and sn-2 positions of glycolipid A, which already contains myristate, and have demonstrated this using inhibitors and a variety of other methods. We have partially characterized myristate exchange with respect to specificity and susceptibility to some inhibitors. The apparent Km for myristoyl CoA is 7 nM. This myristate-specific process may represent a proof-reading system to ensure that the fatty acids on VSG are exclusively myristate. Although myristate exchange was first discovered for glycolipid A, we now believe that VSG is the true substrate of this reaction. VSG is efficiently labeled by exchange in the presence of cycloheximide, which prevents anchoring of newly synthesized protein. Although its location is not yet known, we have evidence that exchange does not localize to either the endoplasmic reticulum or the plasma membrane. We will present data indicating that surface VSG may be internalized and undergo myristate exchange.
L U Buxbaum
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.]     Volume:  27     ISSN:  0100-879X     ISO Abbreviation:  Braz. J. Med. Biol. Res.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-10-13     Completed Date:  1994-10-13     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8112917     Medline TA:  Braz J Med Biol Res     Country:  BRAZIL    
Other Details:
Languages:  eng     Pagination:  115-9     Citation Subset:  IM    
Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21217.
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MeSH Terms
Cell-Free System
Glycosylphosphatidylinositols / biosynthesis*
Myristates / metabolism*
Trypanosoma brucei brucei / chemistry,  metabolism*
Variant Surface Glycoproteins, Trypanosoma / metabolism*
Reg. No./Substance:
0/Glycosylphosphatidylinositols; 0/Myristates; 0/Variant Surface Glycoproteins, Trypanosoma

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