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. 2001 Nov;108(9):1253-9.
doi: 10.1172/JCI14321.

Thyroid autoimmunity

B Rapoport  1 , S M McLachlan
Affiliations

Thyroid autoimmunity

B Rapoport et al. J Clin Invest. 2001 Nov.
No abstract available

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Figures

Figure 1
Figure 1
Schematic representation of the TSHR with its large (397−amino acid residue without signal peptide) ectodomain, seven membrane-spanning segments, and short cytoplasmic tail. TSHR intramolecular cleavage into A and B subunits is associated with the loss of a C peptide region that corresponds approximately to a 50−amino acid “insertion” in the TSHR absent in the noncleaving LH and FSH receptors. The C peptide region is not removed intact. Following cleavage at upstream Site 1, the C peptide is rapidly degraded downstream to the Site 2 region. Evidence suggests that N-terminal degradation of the B subunit continues thereafter, leading to loss of the Cys residues tethering the A subunit and to shedding of the latter. The Cys-rich N-terminus of the A subunit is an important component of thyroid-stimulating autoantibodies and is likely to contain two disulfide bonds (hypothetically shown by dotted lines) contributing to a conformationally important portion of the molecule.
Figure 2
Figure 2
Hypothetical three-dimensional structure of the TPO ectodomain based on the structure of myeloperoxidase (MPO). The ribbon diagram represents one TPO monomer beginning at residue 122 because no structural information is available on the N-terminal 121 amino acid prosequence of MPO (large blue circle), which is removed from the mature molecule. The C-terminus of MPO (“C578”) corresponds to TPO amino acid residue 736. Therefore, the diagram also does not provide insight into the region of the TPO ectodomain extending downstream to its insertion into the plasma membrane (residue 848). Epitopic footprinting identified lysine (K) 713 to be within the epitope of one of the human monoclonal TPO autoantibodies (TR1.9) that define the TPO immunodominant region. This residue is included in the linear epitope (shaded) of mouse mAb no. 47, which is recognized by a small proportion of TPO autoantibodies in an individual patient’s serum (16). Modified, with permission, from refs. , (copyright 2001, The American Association of Immunologists).
See this image and copyright information in PMC

References

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    1. Zeng J, Fenna RE. X-ray crystal structure of canine myeloperoxidase at 3 A resolution. J Mol Biol. 1992;226:185–207. - PubMed

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