2. Academic Validation
  3. Crystal structures of human lysosomal EPDR1 reveal homology with the superfamily of bacterial lipoprotein transporters

Crystal structures of human lysosomal EPDR1 reveal homology with the superfamily of bacterial lipoprotein transporters

  • Commun Biol. 2019 Feb 5;2:52. doi: 10.1038/s42003-018-0262-9.
Yong Wei 1,  Zi Jian Xiong 2,  Jun Li 3,  Chunxia Zou 3,  Christopher W Cairo 3,  John S Klassen 3,  Gilbert G Privé 1 2 4
Affiliations

Affiliations

  • 1 1Princess Margaret Cancer Centre, Toronto, M5G 1L7 ON Canada.
  • 2 2Department of Biochemistry, University of Toronto, Toronto, M5S 1A8 ON Canada.
  • 3 3Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, T6G 2G2 AB Canada.
  • 4 4Department of Medical Biophysics, University of Toronto, Toronto, M5G 1L7 ON Canada.
PMID: 30729188 DOI: 10.1038/s42003-018-0262-9
Abstract

EPDR1, a member of the ependymin-related protein family, is a relatively uncharacterized protein found in the lysosomes and secretomes of most vertebrates. Despite having roles in human disease and health, the molecular functions of EPDR1 remain unknown. Here, we present crystal structures of human EPDR1 and reveal that the protein adopts a fold previously seen only in Bacterial proteins related to the LolA lipoprotein transporter. EPDR1 forms a homodimer with an overall shape resembling a half-shell with two non-overlapping hydrophobic grooves on the flat side of the hemisphere. EPDR1 can interact with membranes that contain negatively charged lipids, including BMP and GM1, and we suggest that EPDR1 may function as a lysosomal activator protein or a lipid transporter. A phylogenetic analysis reveals that the fold is more widely distributed than previously suspected, with representatives identified in all branches of cellular life.

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