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[[ | ==Structure of epidermal growth factor-like repeat 12 of mouse Notch-1 receptor== | ||
<StructureSection load='2rr0' size='340' side='right' caption='[[2rr0]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2rr0]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RR0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RR0 FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1toz|1toz]], [[2joa|2joa]], [[2rqz|2rqz]], [[2rr2|2rr2]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rr0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rr0 RCSB], [http://www.ebi.ac.uk/pdbsum/2rr0 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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, Siaalpha2,3Galbeta1,4GlcNAcbeta1,3Fucalpha1-->. This elongation process is initiated by the action of O-fucose-specific beta1,3 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 beta-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)). | |||
Chemical synthesis, folding, and structural insights into O-fucosylated epidermal growth factor-like repeat 12 of mouse Notch-1 receptor.,Hiruma-Shimizu K, Hosoguchi K, Liu Y, Fujitani N, Ohta T, Hinou H, Matsushita T, Shimizu H, Feizi T, Nishimura S J Am Chem Soc. 2010 Oct 27;132(42):14857-65. PMID:20883017<ref>PMID:20883017</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Fujitani, N.]] | [[Category: Fujitani, N.]] | ||
[[Category: Hosoguchi, K.]] | [[Category: Hosoguchi, K.]] | ||
Revision as of 14:25, 20 October 2014
Structure of epidermal growth factor-like repeat 12 of mouse Notch-1 receptorStructure of epidermal growth factor-like repeat 12 of mouse Notch-1 receptor
Structural highlights
Publication Abstract from PubMedNotch 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, Siaalpha2,3Galbeta1,4GlcNAcbeta1,3Fucalpha1-->. This elongation process is initiated by the action of O-fucose-specific beta1,3 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 beta-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)). Chemical synthesis, folding, and structural insights into O-fucosylated epidermal growth factor-like repeat 12 of mouse Notch-1 receptor.,Hiruma-Shimizu K, Hosoguchi K, Liu Y, Fujitani N, Ohta T, Hinou H, Matsushita T, Shimizu H, Feizi T, Nishimura S J Am Chem Soc. 2010 Oct 27;132(42):14857-65. PMID:20883017[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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