Article
- The EMBO Journal (2002) 21, 504 - 513
- doi:10.1093/emboj/21.4.504
Subject Categories:
Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors
S. Costagliola1, V. Panneels2, M. Bonomi1,3, J. Koch4, M.C. Many5, G. Smits1,6 and G. Vassart1,6
- I.R.I.B.H.N., ULB, 808 Lennik Street, B-1070 Brussels, Belgium
- Structural and Computational Biology Program, EMBL, Heidelberg, Germany
- Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore di Milano IRCCS, Italy
- Institute for Molecular Genetics, University of Heidelberg, Heidelberg, Germany
- Department of Histology, Louvain Medical School, Belgium
- Department of Medical Genetics, ULB, 808 Lennik Street, B-1070 Brussels, Belgium
Correspondence to:
S. Costagliola, E-mail: scostag@ulb.ac.be
Received 10 October 2001; Accepted 21 December 2001; Revised 12 December 2001
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.
Keywords:
- glycoprotein,
- GPCR,
- hormones,
- sulfation,
- tyrosine
