title: High-resolution crystal structure of the human Notch 1 ankyrin domain.
abstract: The Notch receptor is part of a highly conserved signalling system of central importance to animal development. Its ANK (ankyrin) domain is required for Notch-mediated signal transduction. The crystal structure of the human Notch 1 ANK domain was solved by molecular replacement at 1.9 A (1 A=0.1 nm) resolution, and it shows that the features identified in the Drosophila homologue are conserved. The domain has six of the seven ANK repeats predicted from sequence. The putative first repeat, which has only part of the consensus and a long insertion, is disordered in both molecules in the asymmetric unit, possibly due to the absence of the RAM (RBPJkappa-associated molecule) region N-terminal to it. The exposed hydrophobic core is involved in intermolecular interactions in the crystal. Evolutionary trace analysis identified several residues that map to the hairpins of the structure and may be of functional importance. Based on the Notch 1 ANK structure and analysis of homologous Notch ANK sequences, we predict two possible binding sites on the domain: one on the concave surface of repeat 2 and the other below the hairpins of repeats 6-7.
authors: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
authors: Matthias T
authors: MT
authors: Ehebauer
authors: Dimitri Y
authors: DY
authors: Chirgadze
authors: Penny
authors: P
authors: Hayward
authors: Alfonso
authors: A
authors: Martinez Arias
authors: Tom L
authors: TL
authors: Blundell
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051881:Receptor, Notch1 / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1