5KY7

mouse POFUT1 in complex with O-glucosylated EGF(+) and GDP

Summary for 5KY7

• Entry DOI: 10.2210/pdb5ky7/pdb
• Related: 5KXH 5KXQ 5KY0 5KY2 5KY3 5KY4 5KY5 5KY8 5KY9
• Descriptor: GDP-fucose protein O-fucosyltransferase 1, EGF(+), 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: glycosyltransferase, transferase
• Biological source: Mus musculus (Mouse); More
• Cellular location: Endoplasmic reticulum : Q91ZW2
• Total number of polymer chains: 2
• Total formula weight: 45634.48

Authors

Li, Z.,Rini, J.M. (deposition date: 2016-07-21, release date: 2017-05-17, Last modification date: 2024-10-23)

Primary citation

Li, Z.,Han, K.,Pak, J.E.,Satkunarajah, M.,Zhou, D.,Rini, J.M.
Recognition of EGF-like domains by the Notch-modifying O-fucosyltransferase POFUT1.
Nat. Chem. Biol., 13:757-763, 2017

PubMed Abstract: Protein O-fucosyltransferase 1 (POFUT1) fucosylates the epidermal growth factor (EGF)-like domains found in cell-surface and secreted glycoproteins including Notch and its ligands. Although Notch fucosylation is critical for development, and POFUT1 deficiency leads to human disease, how this enzyme binds and catalyzes the fucosylation of its diverse EGF-like domain substrates has not been determined. Reported here is the X-ray crystal structure of mouse POFUT1 in complex with several EGF-like domains, including EGF12 and EGF26 of Notch. Overall shape complementarity, interactions with invariant atoms of the fucosylation motif and flexible segments on POFUT1 all define its EGF-like-domain binding properties. Using large-scale structural and sequence analysis, we also show that POFUT1 binds EGF-like domains of the hEGF type and that the highly correlated presence of POFUT1 and fucosylatable hEGFs has accompanied animal evolution.

PubMed: 28530709
DOI: 10.1038/nchembio.2381

Experimental method

X-RAY DIFFRACTION (1.6 Å)