8E0P

Crystal structure of mouse APCDD1 in fusion with engineered MBP

This is a non-PDB format compatible entry.

Summary for 8E0P

• Entry DOI: 10.2210/pdb8e0p/pdb
• Descriptor: Maltodextrin-binding protein, Protein APCDD1 complex, alpha-D-glucopyranose-(1-4)-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: cell signaling protein, beta barrel, lipid binding protein, signaling protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 4
• Total formula weight: 372508.56

Authors

Hsieh, F.L.,Chang, T.H.,Gabelli, S.B.,Nathans, J. (deposition date: 2022-08-09, release date: 2023-05-03, Last modification date: 2024-11-20)

Primary citation

Hsieh, F.L.,Chang, T.H.,Gabelli, S.B.,Nathans, J.
Structure of WNT inhibitor adenomatosis polyposis coli down-regulated 1 (APCDD1), a cell-surface lipid-binding protein.
Proc.Natl.Acad.Sci.USA, 120:e2217096120-e2217096120, 2023

PubMed Abstract: Diverse extracellular proteins negatively regulate WNT signaling. One such regulator is adenomatosis polyposis coli down-regulated 1 (APCDD1), a conserved single-span transmembrane protein. In response to WNT signaling in a variety of tissues, transcripts are highly up-regulated. We have determined the three-dimensional structure of the extracellular domain of APCDD1, and this structure reveals an unusual architecture consisting of two closely apposed β-barrel domains (ABD1 and ABD2). ABD2, but not ABD1, has a large hydrophobic pocket that accommodates a bound lipid. The APCDD1 ECD can also bind to WNT7A, presumably via its covalently bound palmitoleate, a modification that is common to all WNTs and is essential for signaling. This work suggests that APCDD1 functions as a negative feedback regulator by titrating WNT ligands at the surface of responding cells.

PubMed: 37155902
DOI: 10.1073/pnas.2217096120

Experimental method

X-RAY DIFFRACTION (2.33 Å)