Guanylyl cyclase C (GC-C) is a single-transmembrane receptor that is specifically activated by endogenous ligands, including guanylin, and the exogenous ligand, heat-stable enterotoxin. Using combined HPLC separation and MS analysis techniques the positions of the disulfide linkages in the extracellular ligand-binding domain (ECD) of GC-C were determined to be between Cys7–Cys94, Cys72–Cys77, Cys101–Cys128 and Cys179–Cys226. Furthermore, a three-dimensional structural model of the ECD was constructed by homology modeling, using the structure of the ECD of GC-A as a template (van den Akker et al., 2000, Nature, 406: 101–104) and the information of the disulfide linkages. Although the GC-C model was similar to the known structure of GC-A, importantly its ligand-binding site appears to be located on the quite different region from that in GC-A.
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Abbreviations
- GC:
-
guanylyl cyclase
- ECD:
-
extracellular domain
- STa:
-
heat-stable enterotoxin produced by enterotoxigenic Escherichia coli
- STp(4-17):
-
porcine STa containing the amino acid sequence from position 4 to 17
- ANB:
-
5-azido-2-nitrobezyl
- PNGase-F:
-
peptide-N-glycosidase F
- LC:
-
liquid chromatography
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Hasegawa, M., Matsumoto-Ishikawa, Y., Hijikata, A. et al. Disulfide Linkages and a Three-Dimensional Structure Model of the Extracellular Ligand-binding Domain of Guanylyl Cyclase C. Protein J 24, 315–325 (2005). https://doi.org/10.1007/s10930-005-6752-x
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DOI: https://doi.org/10.1007/s10930-005-6752-x