Klappa, P., Ruddock, L. W., Darby, N. J., and Freedman, R. B. (1998). The b domain provides the principal peptide-binding site of protein disulﬁde isomerase but all domains contribute to binding of misfolded proteins. EMBO J. 17, 927–935. Kozlov, G., Maattanen, P., Schrag, J. D., Hura, G. L., Gabrielli, L., Cygler, M., Thomas, D. Y., and Gehring, K. (2009). Structure of the noncatalytic domains and global fold of the protein disulﬁde isomerase ERp72. Structure 17, 651– 659. Kozlov, G., Maattanen, P., Schrag, J. D., Pollock, S., Cygler, M., Nagar, B., Thomas, D. Y., and Gehring, K. (2006). Crystal structure of the bb’ domains of the protein disulﬁde isomerase ERp57. Structure 14, 1331–1339. Kulp, M. S., Frickel, E. M., Ellgaard, L., and Weissman, J. S. (2006). Domain architecture of protein-disulﬁde isomerase facilitates its dual role as an oxi- dase and an isomerase in Ero1p-mediated disulﬁde formation. J. Biol. Chem. 281, 876 – 884. Laboissiere, M. C., Sturley, S. L., and Raines, R. T. (1995). The essential function of protein-disulﬁde isomerase is to unscramble non-native disulﬁde bonds. J. Biol. Chem. 270, 28006 –28009. Land, A., Zonneveld, D., and Braakman, I. (2003). Folding of HIV-1 envelope glycoprotein involves extensive isomerization of disulﬁde bonds and confor- mation-dependent leader peptide cleavage. FASEB J. 17, 1058 –1067. Lappi, A. K., Lensink, M. F., Alanen, H. I., Salo, K. E., Lobell, M., Juffer, A. H., and Ruddock, L. W. (2004). A conserved arginine plays a role in the catalytic cycle of the protein disulphide isomerases. J. Mol. Biol. 335, 283–295. Lee, S. O., Cho, K., Cho, S., Kim, I., Oh, C., and Ahn, K. (2010). Protein disulphide isomerase is required for signal peptide peptidase-mediated pro- tein degradation. EMBO J. 29, 363–375. Linnik, K. M., and Herscovitz, H. (1998). Multiple molecular chaperones interact with apolipoprotein B during its maturation. The network of endo- plasmic reticulum-resident chaperones (ERp72, GRP94, calreticulin, and BiP) interacts with apolipoprotein b regardless of its lipidation state. J. Biol. Chem. 273, 21368 –21373. Lyles, M. M., and Gilbert, H. F. (1991). Catalysis of the oxidative folding of ribonuclease A by protein disulﬁde isomerase: pre-steady-state kinetics and the utilization of the oxidizing equivalents of the isomerase. Biochemistry 30, 619 – 625. Maruri-Avidal, L., Lopez, S., and Arias, C. F. (2008). Endoplasmic reticulum chaperones are involved in the morphogenesis of rotavirus infectious parti- cles. J. Virol. 82, 5368 –5380. Mazzarella, R. A., Srinivasan, M., Haugejorden, S. M., and Green, M. (1990). ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulﬁde isomerase. J. Biol. Chem. 265, 1094 –1101. Menon, S., Lee, J., Abplanalp, W. A., Yoo, S. E., Agui, T., Furudate, S., Kim, P. S., and Arvan, P. (2007). Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf. J. Biol. Chem. 282, 6183– 6191. Meunier, L., Usherwood, Y. K., Chung, K. T., and Hendershot, L. M. (2002). A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins. Mol. Biol. Cell 13, 4456 – 4469. Mezghrani, A., Fassio, A., Benham, A., Simmen, T., Braakman, I., and Sitia, R. (2001). Manipulation of oxidative protein folding and PDI redox state in mammalian cells. EMBO J. 20, 6288 – 6296. Molinari, M., and Helenius, A. (2000). Chaperone selection during glycopro- tein translocation into the endoplasmic reticulum. Science 288, 331–333. Norgaard, P., Westphal, V., Tachibana, C., Alsoe, L., Holst, B., and Winther, J. R. (2001). Functional differences in yeast protein disulﬁde isomerases. J. Cell Biol. 152, 553–562. Oliver, J. D., Roderick, H. L., Llewellyn, D. H., and High, S. (1999). ERp57 functions as a subunit of speciﬁc complexes formed with the ER lectins calreticulin and calnexin. Mol. Biol. Cell 10, 2573–2582. Oliver, J. D., van der Wal, F. J., Bulleid, N. J., and High, S. (1997). Interaction of the thiol-dependent reductase ERp57 with nascent glycoproteins. Science 275, 86 – 88. Otsu, M., Bertoli, G., Fagioli, C., Guerini-Rocco, E., Nerini-Molteni, S., Ruffato, E., and Sitia, R. (2006). Dynamic retention of Ero1alpha and Ero1beta in the endoplasmic reticulum by interactions with PDI and ERp44. Antioxid. Redox. Signal 8, 274 –282. Oxidative Folding by PDI Family Members Park, B., Lee, S., Kim, E., Cho, K., Riddell, S. R., Cho, S., and Ahn, K. (2006). Redox regulation facilitates optimal peptide selection by MHC class I during antigen processing. Cell 127, 369 –382. Peaper, D. R., Wearsch, P. A., and Cresswell, P. (2005). Tapasin and ERp57 form a stable disulﬁde-linked dimer within the MHC class I peptide-loading complex. EMBO J. 24, 3613–3623. Pirneskoski, A., Klappa, P., Lobell, M., Williamson, R. A., Byrne, L., Alanen, H. I., Salo, K. E., Kivirikko, K. I., Freedman, R. B., and Ruddock, L. W. (2004). Molecular characterization of the principal substrate binding site of the ubiq- uitous folding catalyst protein disulﬁde isomerase. J. Biol. Chem. 279, 10374 – 10381. Rupp, K., Birnbach, U., Lundstrom, J., Van, P. N., and Soling, H. D. (1994). Effects of CaBP2, the rat analog of ERp72, and of CaBP1 on the refolding of denatured reduced proteins. Comparison with protein disulﬁde isomerase. J. Biol. Chem. 269, 2501–2507. Schelhaas, M., Malmstrom, J., Pelkmans, L., Haugstetter, J., Ellgaard, L., Grunewald, K., and Helenius, A. (2007). Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells. Cell 131, 516 –529. Schmidt, B. Z., and Perlmutter, D. H. (2005). Grp78, Grp94, and Grp170 interact with alpha1-antitrypsin mutants that are retained in the endoplasmic reticulum. Am. J. Physiol. Gastrointest. Liver Physiol. 289, G444 –G455. Sevier, C. S., and Kaiser, C. A. (2002). Formation and transfer of disulphide bonds in living cells. Nat. Rev. Mol. Cell Biol. 3, 836 – 847. Sevier, C. S., and Kaiser, C. A. (2008). Ero1 and redox homeostasis in the endoplasmic reticulum. Biochim. Biophys. Acta 1783, 549 –556. Solda, T., Garbi, N., Hammerling, G. J., and Molinari, M. (2006). Conse- quences of ERp57 deletion on oxidative folding of obligate and facultative clients of the calnexin cycle. J. Biol. Chem. 281, 6219 – 6226. Tian, G., Xiang, S., Noiva, R., Lennarz, W. J., and Schindelin, H. (2006). The crystal structure of yeast protein disulﬁde isomerase suggests cooperativity between its active sites. Cell 124, 61–73. Wada, I., Kai, M., Imai, S., Sakane, F., and Kanoh, H. (1997). Promotion of transferrin folding by cyclic interactions with calnexin and calreticulin. EMBO J. 16, 5420 –5432. Walker, K. W., and Gilbert, H. F. (1997). Scanning and escape during protein- disulﬁde isomerase-assisted protein folding. J. Biol. Chem. 272, 8845– 8848. Wang, L., Li, S. J., Sidhu, A., Zhu, L., Liang, Y., Freedman, R. B., and Wang, C. C. (2009). Reconstitution of human Ero1-L{alpha}/protein-disulﬁde isomerase oxidative folding pathway in vitro: Position-dependent differences in role between the a and a domains of protein disulﬁde isomerase. J. Biol. Chem. 284, 199 –206. Weissman, J. S., and Kim, P. S. (1993). Efﬁcient catalysis of disulphide bond rearrangements by protein disulphide isomerase. Nature 365, 185–188. Williams, D. B. (2006). Beyond lectins: the calnexin/calreticulin chaperone system of the endoplasmic reticulum. J. Cell Sci. 119, 615– 623. Wu, J., and Kaufman, R. J. (2006). From acute ER stress to physiological roles of the Unfolded Protein Response. Cell Death Differ. 13, 374 –384. Xiao, R., Wilkinson, B., Solovyov, A., Winther, J. R., Holmgren, A., Lund- strom-Ljung, J., and Gilbert, H. F. (2004). The contributions of protein disul- ﬁde isomerase and its homologues to oxidative protein folding in the yeast endoplasmic reticulum. J. Biol. Chem. 279, 49780 – 49786. Yoshida, H. (2007). Unconventional splicing of XBP-1 mRNA in the unfolded protein response. Antioxid. Redox. Signal 9, 2323–2333. Zapun, A., Darby, N. J., Tessier, D. C., Michalak, M., Bergeron, J. J., and Thomas, D. Y. (1998). Enhanced catalysis of ribonuclease B folding by the interaction of calnexin or calreticulin with ERp57. J. Biol. Chem. 273, 6009 – 6012. Zhang, Y., Baig, E., and Williams, D. B. (2006). Functions of ERp57 in the folding and assembly of major histocompatibility complex class I molecules. J. Biol. Chem. 281, 14622–14631. Zhang, Y., Kozlov, G., Pocanschi, C. L., Brockmeier, U., Ireland, B. S., Maat- tanen, P., Howe, C., Elliott, T., Gehring, K., and Williams, D. B. (2009). ERp57 does not require interactions with calnexin and calreticulin to promote as- sembly of class I histocompatibility molecules, and it enhances peptide load- ing independently of its redox activity. J. Biol. Chem. 284, 10160 –10173. Zheng, L., Baumann, U., and Reymond, J. L. (2004). An efﬁcient one-step site- directed and site-saturation mutagenesis protocol. Nucleic Acids Res. 32, e115. Vol. 21, September 15, 2010 3105