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

DOI: 10.1074/jbc.M110.130427 DOI Help
PMID: 21106528 PMID Help

Authors: Benjamin Moore (Imperial College London) , Andrew J. Miles (Birkbeck College, University of London) , Cristina Guerra-giraldez (University of York) , Peter Simpson (Imperial College London) , Momi Iwata (Diamond Light Source) , B. A. Wallace (Birkbeck College, University of London) , Steven J. Matthews (Imperial College London) , Deborah F. Smith (University of York) , Katherine A. Brown (University of Texas)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry , VOL 286 (11) , PAGES 9246-9256

State: Published (Approved)
Published: January 2011

Open Access Open Access

Abstract: 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.

Subject Areas: Biology and Bio-materials

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