Fig 1.
Schematic showing domain organization of TPO, as determined from sequence analysis.
The protein sequence is coding an N-terminal propeptide domain (yellow), a MPO-like domain (green) with a catalytic heme (red) that is connected to a CCP-like (Shamrock green), and an EGF-like (cyan-blue) domains, an anchoring trans-membrane domain (dark-blue) and an intracellular domain (dark-magenta).
Fig 2.
A comparison between membrane-embedded, dimeric models of TPO isoform1 in two different conformations.
(A) Schematic of trans model with active site facing away from follicular membrane. Coloring as in Fig 1; (B) Cis model with active site facing towards follicular membrane; (C) perpendicular views of trans model; (D) perpendicular views of cis model. TPO represented as cartoon and space filling (subunits A and B, respectively) for clarity. Domains are coloured as follows: MPO-like domain (green), CCP-like domain (Shamrock green), EGF-like domain (cyan-blue), and TM domain (dark-blue). Catalytic heme represented as red spheres, and DMPC molecules represented as lines and coloured as CPK.
Fig 3.
Mapping epitopes onto the trans TPO dimer.
(A) Epitopes and residues identified in various studies as constituting immunodominant regions IDR-A (blue) and IDR-B (pink); (B) Membrane-facing side of MPO-like domain; (C) Close-up shows that much of the two immunodominant regions are on the membrane-facing surface of the MPO-like domain, particularly IDR-B; (D) Lumen-facing side of TPO. Hemes are shown in orange.
Fig 4.
Mapping epitopes onto the cis TPO dimer.
(A) Epitopes and residues identified in various studies as constituting immunodominant regions IDR-A (blue) and IDR-B (pink); (B) Lumen-facing side of MPO-like domain; (C) Close-up shows that much of the two immunodominant regions are on the lumen-facing surface of the MPO-like domain near the dimer interface, particularly IDR-B; (D) Membrane-facing side of TPO containing the heme (orange) cavity.