Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Thyroid-stimulating autoantibodies in Graves disease preferentially recognize the free A subunit, not the thyrotropin holoreceptor
Gregorio D. Chazenbalk, … , Sandra M. McLachlan, Basil Rapoport
Gregorio D. Chazenbalk, … , Sandra M. McLachlan, Basil Rapoport
Published July 15, 2002
Citation Information: J Clin Invest. 2002;110(2):209-217. https://doi.org/10.1172/JCI15745.
View: Text | PDF
Article Aging

Thyroid-stimulating autoantibodies in Graves disease preferentially recognize the free A subunit, not the thyrotropin holoreceptor

  • Text
  • PDF
Abstract

Research Article

Authors

Gregorio D. Chazenbalk, Pavel Pichurin, Chun-Rong Chen, Francesco Latrofa, Alan P. Johnstone, Sandra M. McLachlan, Basil Rapoport

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Schematic representation of different forms of the TSHR. (a) TSH holorec...
Schematic representation of different forms of the TSHR. (a) TSH holoreceptor. Intramolecular cleavage of the single polypeptide chain is followed by removal of the C peptide region, with the A subunit remaining tethered to the membrane-spanning B subunit by disulfide bonds. The cylinders depict the α helices in the nine leucine-rich repeats in the A subunit, as well as the seven transmembrane segments of the B subunit. The ectodomain comprises the entire A subunit and the extracellular region of the B subunit. The ectodomain enters the plasma membrane at approximately amino acid residue 418. A critical domain in the TSAb epitope(s) involves the cysteine-rich area at the extreme N terminus of the TSHR and is shown by the gray oval. (b) TSHR ectodomain tethered to the plasma membrane by a GPI anchor (ECD-GPI). This construct involved the attachment after TSHR codon 412 of a 39–amino acid sequence containing a signal for GPI attachment (31). The putative GPI attachment site of the anchor is at codon 425. Because of the additional length of the ectodomain prior to insertion into the membrane, and because the GPI anchor only traverses the outer leaf of the plasma membrane, the TSHR ectodomain is shown in a more “open” orientation relative to the wild-type TSHR. (c) Shed A subunit. The exact site of cleavage has not been established, but is approximately at amino acid residue 310. The purified TSHR-289 preparation used in this study is truncated at TSHR amino acid residue 289 and therefore comprises nearly the entire A subunit.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts