Structural Basis of Molecular Recognition of the Leishmania Small Hydrophilic Endoplasmic Reticulum-associated Protein (SHERP) at Membrane Surfaces*
Miles, Andrew J.
Wallace, B. A.
Matthews, Stephen J.
Smith, Deborah F.
Brown, Katherine A.
- Publisher: American Society for Biochemistry and Molecular Biology
The Journal of Biological Chemistry,
(issn: 0021-9258, eissn: 1083-351X)
NMR | Parasite | bcs | Leishmania major | Circular Dichroism (CD) | Protein Folding | SHERP | Protein Structure and Folding | Lipid | Vacuolar ATPase | Protein Cross-linking | SRCD, Synchrotron Radiation Circular Dichroism
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.