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Structural basis of molecular recognition of the Leishmania small hydrophilic endoplasmic reticulum-associated protein (SHERP) at membrane surfaces.


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.

SUBMITTER: Moore B 

PROVIDER: S-EPMC3059043 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Structural basis of molecular recognition of the Leishmania small hydrophilic endoplasmic reticulum-associated protein (SHERP) at membrane surfaces.

Moore Benjamin B   Miles Andrew J AJ   Guerra-Giraldez Cristina C   Simpson Peter P   Iwata Momi M   Wallace B A BA   Matthews Stephen J SJ   Smith Deborah F DF   Brown Katherine A KA  

The Journal of biological chemistry 20101124 11


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  ...[more]

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