Crystal Structure and Functional Analysis ofDrosophilaWind, a Protein-disulfide Isomerase-related Protein

Qingjun Ma, Chaoshe Guo, Kathrin Barnewitz, George M. Sheldrick, Hans-Dieter Söling, Isabel Usón, David M. Ferrari
2003 Journal of Biological Chemistry  
In the developing Drosophila melanogaster embryo, dorsal-ventral patterning displays an absolute requirement for the product of the essential windbeutel gene, Wind. In homozygous windbeutel mutant flies, dorsalventral patterning fails to initiate because of the failure of the Golgi-resident proteoglycan-modifying protein, Pipe, to exit the endoplasmic reticulum, and this leads to the death of the embryo. Here, we describe the threedimensional structure of Wind at 1.9-Å resolution and identify a
more » ... tion and identify a candidate surface for interaction with Pipe. This represents the first crystal structure of a eukaryotic protein-disulfide isomerase-related protein of the endoplasmic reticulum to be described. The dimeric protein is composed of an N-terminal thioredoxin domain and a C-terminal ␣-helical domain unique to protein-disulfide isomerase D proteins. Although Wind carries a CXXC motif that is partially surface accessible, this motif is redox inactive, and the cysteines are not required for the targeting of Pipe to the Golgi. However, both domains are required for targeting Pipe to the Golgi, and, although the mouse homologue ERp28 cannot replace the function of Wind, exchange of the Wind D-domain with that of ERp28 allows for efficient Golgi transport of Pipe.
doi:10.1074/jbc.m307966200 pmid:12941941 fatcat:kuvx4hvhfbgyvaqcx5jfcar4zq