Common elements on the surface of glycolytic enzymes from Trypanosoma brucei may serve as topogenic signals for import into glycosomes.
In Trypanosoma brucei, a major pathogenic protozoan parasite of Central Africa, a number of glycolytic enzymes present in the cytosol of other organisms are uniquely segregated in a microbody-like organelle, the glycosome, which they are believed to reach post-translationally after being synthesized by free ribosomes in the cytosol. In a search for possible topogenic signals responsible for import into glycosomes we have compared the amino acid sequences of four glycosomal enzymes: triosephosphate isomerase (TIM), glyceraldehyde-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK) and aldolase (ALDO), with each other and with their cytosolic counterparts. Each of these enzymes contains a marked excess of positive charges, distributed in two or more clusters along the polypeptide chain. Modelling of the three-dimensional structures of TIM, PGK and GAPDH using the known structural coordinates of homologous enzymes from other organisms indicates that all three may have in common two 'hot spots' about 40 A apart, which themselves include a pair of basic amino acid residues separated by a distance of about 7 A. The sequence of glycosomal ALDO, for which no three-dimensional information is available, is compatible with the presence of the same configuration on the surface of this enzyme. We propose that this feature plays an essential role in the import of enzymes into glycosomes.
D000595:Amino Acid Sequence; D000818:Animals; D002238:Carbohydrate Epimerases / Q000235:genetics*; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006019:Glycolysis; D008830:Microbodies / Q000201:enzymology*; D008958:Models, Molecular; D010735:Phosphoglycerate Kinase / Q000235:genetics; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D014305:Triose-Phosphate Isomerase / Q000235:genetics*; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics
D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010735:Phosphoglycerate Kinase; D005634:Fructose-Bisphosphate Aldolase; D002238:Carbohydrate Epimerases; D014305:Triose-Phosphate Isomerase