The structure of FCGBP is formed as a disulfide‐mediated homodimer between its C‐terminal domains

• DOI: 10.1111/febs.17383
• Publication Date: 2025-01-04T04:22:09Z
• Authors: Erik Ehrencrona; Pablo Gallego; Sergio Trillo‐Muyo; Maria‐Jose Garcia...; Christian V. Reck...; Gunnar C. Hansson; Malin E. V. Johan...
• Keywords: Trimer

Mucus in the colon is crucial for intestinal homeostasis by forming a barrier that separates microbes from epithelium. This achieved structural arrangement of major mucus proteins, such as MUC2 and FCGBP, both which are comprised several von Willebrand D domains (vWD) assemblies. Numerous disulfide bonds stabilise these domains, intermolecular generate multimers MUC2. The oligomeric nature FCGBP not known. Human hFCGBP contains 13 vWD whereas mouse mFCGBP consists only 7. We found unpaired cysteines vWD1 (human mouse) vWD5 (mouse)/vWD11 (human) assemblies were involved bonds. However, most C‐terminal vWD7 (mouse)/vWD13 (human), formed disulfide‐linked dimers. bond between C 5284 5403 human was observed using mass spectrometry to dimer. Cryo‐EM structure analysis recombinant revealed compact dimer with two symmetric 2462 2581 , corresponding dimerising hFCGBP. conformation involves interactions assemblies, but although at interface same, differ. Mouse also exist semi‐extended conformation. These different offer insights into dynamic homodimer.