A helical membrane-binding domain targets the Toxoplasma ROP2 family to the parasitophorous vacuole

Traffic. 2009 Oct;10(10):1458-70. doi: 10.1111/j.1600-0854.2009.00958.x. Epub 2009 Jun 22.

Abstract

During invasion, the obligate intracellular pathogen, Toxoplasma gondii, secretes into its host cell a variety of effector molecules, several of which have been implicated in strain-specific variation in disease. The largest family of these effectors, defined by the canonical member ROP2, quickly associates with the nascent parasitophorous vacuole membrane (PVM) after secretion. Here we demonstrate that the NH(2)-terminal domain of the ROP2 family contains a series of amphipathic helices that are necessary and sufficient for membrane association. While each of the amphipathic helices is individually competent to bind cellular membranes, together they act to bind the PVM preferentially, possibly through sensing its strong negative curvature. This previously uncharacterized helical domain is an evolutionarily robust and energetically efficient design for membrane association.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Cell Line
  • Conserved Sequence
  • Cytosol / metabolism
  • Cytosol / parasitology
  • Fibroblasts / metabolism
  • Fibroblasts / parasitology
  • Host-Parasite Interactions
  • Humans
  • Intracellular Membranes / metabolism*
  • Intracellular Membranes / parasitology
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • Protein Transport
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Spectrometry, Fluorescence
  • Toxoplasma / metabolism*
  • Vacuoles / metabolism*
  • Vacuoles / parasitology

Substances

  • Membrane Proteins
  • Protozoan Proteins
  • ROP 2 protein, Toxoplasma gondii