title: 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.
authors.affiliation: Division of Cell and Molecular Biology, Centre for Molecular Microbiology and Infection, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Moore
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Miles
authors.forename: Cristina
authors.initials: C
authors.lastname: Guerra-Giraldez
authors.forename: Peter
authors.initials: P
authors.lastname: Simpson
authors.forename: Momi
authors.initials: M
authors.lastname: Iwata
authors.forename: B A
authors.initials: BA
authors.lastname: Wallace
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Matthews
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Smith
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Brown
mesh_terms: D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics; D018320:Leishmania major / Q000201:enzymology* / Q000235:genetics; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D025262:Vacuolar Proton-Translocating ATPases