"AbstractProtein disulfide isomerases (PDIs) family members are essential for proper folding of proteins entering the secretory pathway. Studies of these remarkable enzymes have shown that PDIs catalyze the oxidation, reduction and isomeration of disulfide bonds in the endoplasmic reticulum (ER). PDIs are found and conserved in a wide range of species and are ubiquitously expressed.In all eukaryotes, the ER redox potential must be tightly controlled since a large fraction of proteins within the cell require disulfide-bond formation. How PDIA1 maintains a balance between oxidation and reduction remains an important open question. Previous studies have revealed the tendency of PDIA1 to dimerize, but little is known about the functional relevance of PDIA1 dimerization. Also a recent crystal structure of a dimeric form of human PDIA1 shows that the formation of dimers inhibits substrate binding and therefore may function as a mechanism to regulate PDIA1 activity in the ER. This thesis has found that PDIA1 dimerizes in vivo and proposes that the dimerization of PDIA1 has physiological relevance by auto-regulating its activity. This mechanism would allow the ER to maintain a balance between oxidation and reduction necessary for native disulfide formation. Another enzyme, PDILT, is a testis-specific PDI. PDILT shares a high sequence similarity (32% identity) with PDIA1. Previous studies suggest that they share the same mechanism for binding substrates, which is mediated by a highly conserved hydrophobic pocket. In this thesis, the crystal structure of the PDILT b'-domain is reported and reveals a hydrophobic pocket that contains interesting features for substrate binding. Structural studies of this new PDI-member will help to understand the important role that PDILT plays in the differentiation and maturation on spermatozoids. The study of ER protein folding in the testis may lead to the identification of proteins and pathways associated with male infertility. " --