1ot8

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spinqualitylabelsall models 1ot8, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of the Ankyrin Domain of the Drosophila Notch Receptor

Overview

The Notch receptor contains a conserved ankyrin repeat domain that is, required for Notch-mediated signal transduction. The ankyrin domain of, Drosophila Notch contains six ankyrin sequence repeats previously, identified as closely matching the ankyrin repeat consensus sequence, and, a putative seventh C-terminal sequence repeat that exhibits lower, similarity to the consensus sequence. To better understand the role of the, Notch ankyrin domain in Notch-mediated signaling and to examine how, structure is distributed among the seven ankyrin sequence repeats, we have, determined the crystal structure of this domain to 2.0 angstroms, resolution. The seventh, C-terminal, ankyrin sequence repeat adopts a, regular ankyrin fold, but the first, N-terminal ankyrin repeat, which, contains a 15-residue insertion, appears to be largely disordered. The, structure reveals a substantial interface between ankyrin polypeptides, showing a high degree of shape and charge complementarity, which may be, related to homotypic interactions suggested from indirect studies., However, the Notch ankyrin domain remains largely monomeric in solution, demonstrating that this interface alone is not sufficient to promote tight, association. Using the structure, we have classified reported mutations, within the Notch ankyrin domain that are known to disrupt signaling into, those that affect buried residues and those restricted to surface, residues. We show that the buried substitutions greatly decrease protein, stability, whereas the surface substitutions have only a marginal affect, on stability. The surface substitutions are thus likely to interfere with, Notch signaling by disrupting specific Notch-effector interactions and map, the sites of these interactions.

About this Structure

1OT8 is a Single protein structure of sequence from Drosophila melanogaster with MG as ligand. Full crystallographic information is available from OCA.

Reference

Structure and stability of the ankyrin domain of the Drosophila Notch receptor., Zweifel ME, Leahy DJ, Hughson FM, Barrick D, Protein Sci. 2003 Nov;12(11):2622-32. PMID:14573873

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