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Structural and functional properties of the human Notch-1 ligand binding region

Hambleton, Sophie, Valeyev, Najl V., Muranyi, Andreas, Knott, Vroni, Werner, Jorn M., McMichael, Andrew J., Handford, Penny A. and Downing, A. Kristina (2004) Structural and functional properties of the human Notch-1 ligand binding region Structure, 12, (12), pp. 2173-2183.

Record type: Article


We present NMR structural and dynamics analysis of the putative ligand binding region of human Notch-1, comprising EGF-like domains 11–13. Functional integrity of an unglycosylated, recombinant fragment was confirmed by calcium-dependent binding of tetrameric complexes to ligand-expressing cells. EGF modules 11 and 12 adopt a well-defined, rod-like orientation rigidified by calcium. The interdomain tilt is similar to that found in previously studied calcium binding EGF pairs, but the angle of twist is significantly different. This leads to an extended double-stranded ? sheet structure, spanning the two EGF modules. Based on the conservation of residues involved in interdomain hydrophobic packing, we propose this arrangement to be prototypical of a distinct class of EGF linkages. On this premise, we have constructed a model of the 36 EGF modules of the Notch extracellular domain that enables predictions to be made about the general role of calcium binding to this region.

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Published date: December 2004


Local EPrints ID: 56697
ISSN: 0969-2126
PURE UUID: ae1f5834-bfcd-4f75-968c-dfd40e14aff4
ORCID for Jorn M. Werner: ORCID iD

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Date deposited: 08 Aug 2008
Last modified: 17 Jul 2017 14:30

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Author: Sophie Hambleton
Author: Najl V. Valeyev
Author: Andreas Muranyi
Author: Vroni Knott
Author: Jorn M. Werner ORCID iD
Author: Andrew J. McMichael
Author: Penny A. Handford
Author: A. Kristina Downing

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