Structural highlights
Function
RUMI_DROME Protein O-glucosyltransferase. Catalyzes the reaction that attaches glucose through an O-glycosidic linkage to a conserved serine residue in epidermal growth factor-like repeats. Regulates Notch signaling by glucosylating Notch in the ER, glucosylation is required for the correct folding and cleavage of Notch.[1]
Publication Abstract from PubMed
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.
Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations.,Yu H, Takeuchi H, Takeuchi M, Liu Q, Kantharia J, Haltiwanger RS, Li H Nat Chem Biol. 2016 Sep;12(9):735-40. doi: 10.1038/nchembio.2135. Epub 2016 Jul, 18. PMID:27428513[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Acar M, Jafar-Nejad H, Takeuchi H, Rajan A, Ibrani D, Rana NA, Pan H, Haltiwanger RS, Bellen HJ. Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell. 2008 Jan 25;132(2):247-58. doi: 10.1016/j.cell.2007.12.016. PMID:18243100 doi:http://dx.doi.org/10.1016/j.cell.2007.12.016
- ↑ Yu H, Takeuchi H, Takeuchi M, Liu Q, Kantharia J, Haltiwanger RS, Li H. Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations. Nat Chem Biol. 2016 Sep;12(9):735-40. doi: 10.1038/nchembio.2135. Epub 2016 Jul, 18. PMID:27428513 doi:http://dx.doi.org/10.1038/nchembio.2135
