Figure 5.

Preferential cleavage sites for cysteine cathepsins within the thyroglobulin sequence at distinct redox- and pH-conditions. Characteristic Tg-fragments obtained by in vitro degradation at extracellular or intra-endo-lysosomal conditions were N-terminally sequenced. Newly generated N-termini are highlighted (A); box colors represent the respective condition at which fragments were obtained (c.f. Figure 1). Hormogenic sites, i.e. pre-formed thyroid hormones tri-iodothyronine (T3) and thyroxine (T4), are tagged in blue and green; the signal peptide is highlighted in grey. (B-D) Schematic drawings sketch the Tg molecule that comprises Tg Type I domains (green), Type II (blue), Type III A (light grey), Type III B repeats (dark grey), Thyropins (red), and CXXC-motifs (see [6] for details). Arrowheads indicate relative positions of identified cleavage sites utilized in extracellular- (B) or endosomal-like Tg processing (C). Cleavage sites of cathepsins B, D, and L were determined by N-terminal sequencing of Tg fragments derived from incubation of rabbit Tg with lysosomal extracts or cathepsins isolated from human thyrocytes (D; according to [36,37]). This scheme (D) is shown for comparison, only, and shaded to indicate that it is adopted (see [6]) from the results of studies performed by Dunn and co-workers [36,37]. Corresponding cysteine cathepsins or combinations thereof are given below the arrowheads; the respective neo-N-termini are specified above the representative schematic drawing. Arrows in B and D indicate similar cleavage sites under extracellular conditions and within lysosomes, respectively.

Jordans et al. BMC Biochemistry 2009 10:23   doi:10.1186/1471-2091-10-23
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