3boa
Crystal structure of yeast protein disulfide isomerase.
Structural highlights
FunctionPDI_YEAST Protein disulfide isomerase of ER lumen required for formation of disulfide bonds in secretory and cell-surface proteins and which unscrambles non-native disulfide bonds. Forms a complex with MNL1 to process unfolded protein-bound Man8GlcNAc2 oligosaccharides to Man7GlcNAc2, promoting degradation in unfolded protein response.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedProtein-disulfide isomerase (PDI) catalyzes the formation of the correct pattern of disulfide bonds in secretory proteins. A low resolution crystal structure of yeast PDI described here reveals large scale conformational changes compared with the initially reported structure, indicating that PDI is a highly flexible molecule with its catalytic domains, a and a', representing two mobile arms connected to a more rigid core composed of the b and b' domains. Limited proteolysis revealed that the linker between the a domain and the core is more susceptible to degradation than that connecting the a' domain to the core. By restricting the two arms with inter-domain disulfide bonds, the molecular flexibility of PDI, especially that of its a domain, was demonstrated to be essential for the enzymatic activity in vitro and in vivo. The crystal structure also featured a PDI dimer, and a propensity to dimerize in solution and in the ER was confirmed by cross-linking experiments and the split green fluorescent protein system. Although sedimentation studies suggested that the self-association of PDI is weak, we hypothesize that PDI exists as an interconvertible mixture of monomers and dimers in the endoplasmic reticulum due to its high abundance in this compartment. The catalytic activity of protein-disulfide isomerase requires a conformationally flexible molecule.,Tian G, Kober FX, Lewandrowski U, Sickmann A, Lennarz WJ, Schindelin H J Biol Chem. 2008 Nov 28;283(48):33630-40. Epub 2008 Sep 24. PMID:18815132[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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