Structures of Type 2 Peroxisomal Targeting Signals in Two Trypanosomatid Aldolases

J Mol Biol. 2000 Jul 21;300(4):697-707. doi: 10.1006/jmbi.2000.3910.

Abstract

Trypanosomatids, unicellular organisms responsible for several global diseases, contain unique organelles called glycosomes in which the first seven glycolytic enzymes are sequestered. We report the crystal structures of glycosomal fructose-1,6-bisphosphate aldolase from two major tropical pathogens, Trypanosoma brucei and Leishmania mexicana, the causative agents of African sleeping sickness and one form of leishmaniasis, respectively. Unlike mammalian aldolases, the T. brucei and L. mexicana aldolases contain nonameric N-terminal type 2 peroxisomal targeting signals (PTS2s) to direct their import into the glycosome. In both tetrameric trypanosomatid aldolases, the PTS2s from two different subunits form two closely intertwined structures. These "PTS2 dimers", which have very similar conformations in the two aldolase structures, are the first reported conformations of a glycosomal or peroxisomal PTS2, and provide opportunities for the design of trypanocidal compounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Crystallography, X-Ray
  • Dimerization
  • Fructose-Bisphosphate Aldolase / chemistry*
  • Fructose-Bisphosphate Aldolase / metabolism*
  • Hydrogen Bonding
  • Leishmania mexicana / enzymology*
  • Models, Molecular
  • Molecular Sequence Data
  • Peroxisomes / metabolism*
  • Protein Sorting Signals / chemistry*
  • Protein Sorting Signals / physiology
  • Protein Structure, Quaternary
  • Sequence Alignment
  • Trypanosoma brucei brucei / enzymology*

Substances

  • Protein Sorting Signals
  • Fructose-Bisphosphate Aldolase

Associated data

  • PDB/1EPX
  • PDB/1F27