Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors

S. Costagliola, V. Panneels, M. Bonomi, J. Koch, M. C. Many, G. Smits, G. Vassart

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

The glycoprotein hormone receptors (thyrotrophin receptor, TSHr; luteinizing hormone/chorionic gonadotrophin receptor, LH/CGr; follicle-stimulating hormone receptor, FSHr) constitute a subfamily of rhodopsin-like G protein-coupled receptors (GPCRs) with a long N-terminal extracellular extension responsible for high-affinity hormone binding. These ectodomains contain two cysteine clusters flanking nine leucine-rich repeats (LRR), a motif found in several protein families involved in protein-protein interactions. Similar to the situation described recently in CCR5, we demonstrate here that the TSHr, as it is present at the cell surface, is sulfated on tyrosines in a motif located downstream of the C-terminal cysteine cluster. Sulfation of one of the two tyrosines in the motif is mandatory for high-affinity binding of TSH and activation of the receptor. Site-directed mutagenesis experiments indicate that the motif, which is conserved in all members of the glycoprotein hormone receptor family, seems to play a similar role in the LH/CG and FSH receptors.

Original languageEnglish
Pages (from-to)504-513
Number of pages10
JournalEMBO Journal
Volume21
Issue number4
DOIs
Publication statusPublished - Feb 15 2002

Fingerprint

FSH Receptors
Tyrosine
LH Receptors
Glycoproteins
Hormones
Cysteine
Thyrotropin Receptors
Mutagenesis
Proteins
Rhodopsin
Thyrotropin
Luteinizing Hormone
G-Protein-Coupled Receptors
Site-Directed Mutagenesis
Leucine
Chemical activation
Experiments

Keywords

  • Glycoprotein
  • GPCR
  • Hormones
  • Sulfation
  • Tyrosine

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Costagliola, S., Panneels, V., Bonomi, M., Koch, J., Many, M. C., Smits, G., & Vassart, G. (2002). Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors. EMBO Journal, 21(4), 504-513. https://doi.org/10.1093/emboj/21.4.504

Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors. / Costagliola, S.; Panneels, V.; Bonomi, M.; Koch, J.; Many, M. C.; Smits, G.; Vassart, G.

In: EMBO Journal, Vol. 21, No. 4, 15.02.2002, p. 504-513.

Research output: Contribution to journalArticle

Costagliola, S, Panneels, V, Bonomi, M, Koch, J, Many, MC, Smits, G & Vassart, G 2002, 'Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors', EMBO Journal, vol. 21, no. 4, pp. 504-513. https://doi.org/10.1093/emboj/21.4.504
Costagliola, S. ; Panneels, V. ; Bonomi, M. ; Koch, J. ; Many, M. C. ; Smits, G. ; Vassart, G. / Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors. In: EMBO Journal. 2002 ; Vol. 21, No. 4. pp. 504-513.
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