5F86

Crystal structure of Drosophila Poglut1 (Rumi) complexed with its substrate protein (EGF repeat)

Summary for 5F86

• Entry DOI: 10.2210/pdb5f86/pdb
• Related: 5F84 5F85 5F87
• Descriptor: O-glucosyltransferase rumi, Coagulation factor IX, GLYCEROL, ... (5 entities in total)
• Functional Keywords: glycosyltransferase, protein o-glucosyltransferase, notch regulation, egf repeat, transferase-hydrolase complex, transferase/hydrolase
• Biological source: Drosophila melanogaster (Fruit fly); More
• Cellular location: Endoplasmic reticulum lumen : Q8T045; Secreted : P00740
• Total number of polymer chains: 2
• Total formula weight: 53198.87

Authors

Yu, H.J.,Li, H.L. (deposition date: 2015-12-09, release date: 2016-07-20, Last modification date: 2024-10-16)

Primary citation

Yu, H.,Takeuchi, H.,Takeuchi, M.,Liu, Q.,Kantharia, J.,Haltiwanger, R.S.,Li, H.
Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations.
Nat. Chem. Biol., 12:735-740, 2016

PubMed Abstract: Rumi O-glucosylates the EGF repeats of a growing list of proteins essential in metazoan development, including Notch. Rumi is essential for Notch signaling, and Rumi dysregulation is linked to several human diseases. Despite Rumi's critical roles, it is unknown how Rumi glucosylates a serine of many but not all EGF repeats. Here we report crystal structures of Drosophila Rumi as binary and ternary complexes with a folded EGF repeat and/or donor substrates. These structures provide insights into the catalytic mechanism and show that Rumi recognizes structural signatures of the EGF motif, the U-shaped consensus sequence, C-X-S-X-(P/A)-C and a conserved hydrophobic region. We found that five Rumi mutations identified in cancers and Dowling-Degos disease are clustered around the enzyme active site and adversely affect its activity. Our study suggests that loss of Rumi activity may underlie these diseases, and the mechanistic insights may facilitate the development of modulators of Notch signaling.

PubMed: 27428513
DOI: 10.1038/nchembio.2135

Experimental method

X-RAY DIFFRACTION (1.9 Å)