title: Structure of the substrate-binding b' domain of the Protein Disulfide Isomerase-Like protein of the Testis.
abstract: Protein Disulfide Isomerase-Like protein of the Testis (PDILT) is a testis-specific member of the PDI family. PDILT displays similar domain architecture to PDIA1, the founding member of this protein family, but lacks catalytic cysteines needed for oxidoreduction reactions. This suggests special importance of chaperone activity of PDILT, but how it recognizes misfolded protein substrates is unknown. Here, we report the high-resolution crystal structure of the b' domain of human PDILT. The structure reveals a conserved hydrophobic pocket, which is likely a principal substrate-binding site in PDILT. In the crystal, this pocket is occupied by side chains of tyrosine and tryptophan residues from another PDILT molecule, suggesting a preference for binding exposed aromatic residues in protein substrates. The lack of interaction of the b' domain with the P-domains of calreticulin-3 and calmegin hints at a novel way of interaction between testis-specific lectin chaperones and PDILT. Further studies of this recently discovered PDI member would help to understand the important role that PDILT plays in the differentiation and maturation of spermatozoids.
authors.affiliation: Department of Biochemistry, Groupe de recherche axé sur la structure des protéines, McGill University, 3649 Promenade Sir William Osler, Montréal, Québec, Canada H3G 0B1.
authors.forename: Sara
authors.initials: S
authors.lastname: Bastos-Aristizabal
authors.affiliation: Department of Biochemistry, Groupe de recherche axé sur la structure des protéines, McGill University, 3649 Promenade Sir William Osler, Montréal, Québec, Canada H3G 0B1.
authors.forename: Guennadi
authors.initials: G
authors.lastname: Kozlov
authors.affiliation: Department of Biochemistry, Groupe de recherche axé sur la structure des protéines, McGill University, 3649 Promenade Sir William Osler, Montréal, Québec, Canada H3G 0B1.
authors.forename: Kalle
authors.initials: K
authors.lastname: Gehring
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics*; D018360:Crystallography, X-Ray; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D037102:Lectins / Q000737:chemistry; D008297:Male; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D013094:Spermatozoa / Q000254:growth & development; D013737:Testis / Q000737:chemistry*
chemical_list: D037102:Lectins; C496702:PDILT protein, human; D019704:Protein Disulfide-Isomerases