Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors.
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.
Costagliola
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S
I.R.I.B.H.N. and Department of Medical Genetics, ULB, 808 Lennik Street, B-1070 Brussels, Belgium. scostag@ulb.ac.be
Panneels
V
V
Bonomi
M
M
Koch
J
J
Many
M C
MC
Smits
G
G
Vassart
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013464:Sulfuric Acids / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D011956:Receptors, Cell Surface; D013464:Sulfuric Acids; D014443:Tyrosine