title: The crystal structure of the protein-disulfide isomerase family member ERp27 provides insights into its substrate binding capabilities.
abstract: About one-third of all cellular proteins pass through the secretory pathway and hence undergo oxidative folding in the endoplasmic reticulum (ER). Protein-disulfide isomerase (PDI) and related members of the PDI family assist in the folding of substrates by catalyzing the oxidation of two cysteines and isomerization of disulfide bonds as well as by acting as chaperones. In this study, we present the crystal structure of ERp27, a redox-inactive member of the PDI family. The structure reveals its substrate-binding cleft, which is homologous to PDI, but is able to adapt in size and hydrophobicity. Isothermal titration calorimetry experiments demonstrate that ERp27 is able to distinguish between folded and unfolded substrates, only interacting with the latter. ERp27 is up-regulated during ER stress, thus presumably allowing it to bind accumulating misfolded substrates and present them to ERp57 for catalysis.
authors.affiliation: Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany.
authors.forename: Franz-Xaver
authors.initials: FX
authors.lastname: Kober
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koelmel
authors.forename: Jochen
authors.initials: J
authors.lastname: Kuper
authors.forename: Johannes
authors.initials: J
authors.lastname: Drechsler
authors.forename: Christine
authors.initials: C
authors.lastname: Mais
authors.forename: Heike M
authors.initials: HM
authors.lastname: Hermanns
authors.forename: Hermann
authors.initials: H
authors.lastname: Schindelin
mesh_terms: D001665:Binding Sites; D055162:Biocatalysis; D002151:Calorimetry; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D000097795:ATPase Inhibitory Protein
chemical_list: D004220:Disulfides; D018832:Molecular Chaperones; D019704:Protein Disulfide-Isomerases; D011506:Proteins; D000097795:ATPase Inhibitory Protein