Moore, B. and Miles, Andrew J. and Guerra-Giraldez, C. and Simpson, P. and Iwata, M. and Wallace, Bonnie A. and Matthews, S.J. and Smith, D.F. and Brown, K.A. (2011) Structural basis of molecular recognition of the Leishmania Small Hydrophilic Endoplasmic Reticulum-associated Protein (SHERP) at membrane surfaces. Journal of Biological Chemistry 286 (11), pp. 9246-9256. ISSN 0021-9258.
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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.
|Keyword(s) / Subject(s):||Circular Dichroism (CD), lipid, NMR, parasite, protein cross-linking, protein folding, vacuolar ATPase, Leishmania major, SHERP, SRCD, Synchrotron Radiation Circular Dichroism|
|School or Research Centre:||Birkbeck Schools and Research Centres > School of Science > Biological Sciences|
|Date Deposited:||20 Jun 2011 14:44|
|Last Modified:||17 Apr 2013 12:33|
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