2RR2

Structure of O-fucosylated epidermal growth factor-like repeat 12 of mouse Notch-1 receptor

2RR2 の概要

• エントリーDOI: 10.2210/pdb2rr2/pdb
• 関連するPDBエントリー: 1TOZ 2JOA 2RQZ 2RR0
• 分子名称: Neurogenic locus notch homolog protein 1, alpha-L-fucopyranose (2 entities in total)
• 機能のキーワード: notch, glycopeptide, o-linked fucose, fringe, egf-like domain, activator, ank repeat, cell membrane, developmental protein, differentiation, disulfide bond, glycoprotein, metal-binding, notch signaling pathway, nucleus, phosphoprotein, receptor, transcription, transcription regulation, transmembrane
• 由来する生物種: Mus musculus (MOUSE)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4382.85

構造登録者

Hosoguchi, K.,Shimizu, K.,Fujitani, N.,Nishimura, S. (登録日: 2010-02-26, 公開日: 2010-10-13, 最終更新日: 2024-10-16)

主引用文献

Hiruma-Shimizu, K.,Hosoguchi, K.,Liu, Y.,Fujitani, N.,Ohta, T.,Hinou, H.,Matsushita, T.,Shimizu, H.,Feizi, T.,Nishimura, S.
Chemical Synthesis, Folding, and Structural Insights into O-Fucosylated Epidermal Growth Factor-like Repeat 12 of Mouse Notch-1 Receptor
J.Am.Chem.Soc., 132:14857-14865, 2010

PubMed Abstract: Notch receptors are cell surface glycoproteins that play key roles in a number of developmental cascades in metazoa. The extracellular domains of Notch-1 receptors are composed of 36 tandem epidermal growth factor (EGF)-like repeats, many of which are modified at highly conserved consensus sites by an unusual form of O-glycan, with O-fucose. The O-fucose residues on certain EGF repeats may be elongated. In mammalian cells this can be a tetrasaccharide, Siaα2,3Galβ1,4GlcNAcβ1,3Fucα1→. This elongation process is initiated by the action of O-fucose-specific β1,3 N-acetylglucosaminyltransferases of the Fringe family. There is evidence that the addition of GlcNAc by Fringe serves as an essential modulator of the interaction of Notch with its ligands and the triggering of activation. Here we describe the efficient synthesis, folding, and structural characterization of EGF repeat 12 (EGF 12) of a mouse Notch-1 receptor bearing different O-fucose glycan chains. We demonstrate that the three disulfide bonds, Cys(456)-Cys(467) (C1-C3), Cys(461)-Cys(476) (C2-C4), and Cys(478)-Cys(487) (C5-C6) were correctly formed in the nonglycosylated as well as the O-fucosylated forms of EGF 12. Three-dimensional structural studies by NMR reveal that the methyl group of fucose is in close contact with ILe(475), Met(477), Pro(478) residues and this stabilizes the conformation of the antiparallel β-sheet of EGF 12. The addition of the GlcNAc residue on O-fucosylated EGF 12 induces a significant conformational change in the adjacent tripeptide sequence, Gln(462)Asn(463)Asp(464), which is a motif involved in the natural, enzymatic O-fucosylation at the conserved site (Cys(461)X(4)Ser/ThrCys(467)).

PubMed: 20883017
DOI: 10.1021/ja105216u

実験手法

SOLUTION NMR