Structural Basis of Molecular Recognition of the Leishmania Small Hydrophilic Endoplasmic Reticulum-associated Protein (SHERP) at Membrane Surfaces

Benjamin Moore, Andrew J. Miles, Cristina Guerra-Giraldez, Peter Simpson, Momi Iwata, B. A. Wallace, Stephen J. Matthews, Deborah F. Smith, Katherine A. Brown

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The 57-residue small hydrophilic endoplasmic reticulum-associated protein (SHERP) shows highly specific, stage-regulated expression in the non-replicative vector-transmitted stages of the kinetoplastid parasite, Leishmania major, the causative agent of human cutaneous leishmaniasis. Previous studies have demonstrated that SHERP localizes as a peripheral membrane protein on the cytosolic face of the endoplasmic reticulum and on outer mitochondrial membranes, whereas its high copy number suggests a critical function in vivo. However, the absence of defined domains or identifiable orthologues, together with lack of a clear phenotype in transgenic parasites lacking SHERP, has limited functional understanding of this protein. Here, we use a combination of biophysical and biochemical methods to demonstrate that SHERP can be induced to adopt a globular fold in the presence of anionic lipids or SDS. Cross-linking and binding studies suggest that SHERP has the potential to form a complex with the vacuolar type H+-ATPase. Taken together, these results suggest that SHERP may function in modulating cellular processes related to membrane organization and/or acidification during vector transmission of infective Leishmania.

Original languageEnglish
Pages (from-to)9246-9256
Number of pages11
JournalJournal of Biological Chemistry
Issue number11
Publication statusPublished - 18 Mar 2011


  • Endoplasmic Reticulum
  • Leishmania major
  • Protein Folding
  • Protein Structure, Tertiary
  • Protozoan Proteins
  • Vacuolar Proton-Translocating ATPases

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