Figure 2: NMR solution structure of rDc1a.

(a) Stereo view of the ensemble of 20 rDc1a structures. The structures are overlaid over the backbone atoms of residues 2–42 and 52–56 in order to highlight the disordered nature of the hairpin loop (residues 43–51, purple) relative to the well-structured ICK region of the toxin. The N and C termini are labelled and the β-strands that form the N- and C-terminal β-sheets are coloured blue and green, respectively. (b) Ribbon representation of rDc1a highlighting the five β- strands (β1–β5) and four disulphide bonds. The three disulphide bonds that form the ICK motif are shown in red while the fourth disulphide that staples the base of the disordered β4–β5 hairpin loop is highlighted in orange. The β-strands and disordered hairpin loop are coloured as in a. (c) Stereo view of the structures of As1a, a typical knottin peptide³⁰, overlaid with rDc1a. The two structures were overlaid for optimal superposition over their core ICK regions (28 residues; region highlighted in cyan) using the CLICK server⁷⁰. Note that the N-terminal β-sheet in rDc1a is quite distinct from the region of structural overlap. (d) Electrostatic surface potential of rDc1a with positive and negative charges shown in blue and red, respectively. The molecular orientation is the same as in panels a and c.