Follicle Stimulating Hormone (FSH) in complex with Follicle Stimulating Hormone Receptor (FSHR)

1
Follicle Stimulating Hormone (FSH)in complex
with Follicle Stimulating Hormone Receptor
(FSHR)

• FSH is central to reproduction in vertebrates
• FSH is produced and secreted by the
  gonadotrophes of the anterior pituitary gland.
• In the ovaries it stimulates the maturation of
  Graafian follicles from which a mature,
  fertilizable oocyte is released
• In the testes enhances the production of
  androgen-binding protein and maintains
  spermatogenesis
• FSHR is G protein-coupled receptors (GPCR)
• Has large extracellular domain
• Does not contain Asp-Arg-Tyr triplet motif

2
FSH (a and ß domains) - FSHR (extracellular
domain)

• Early evidence FSH on murine and bovine testes
  induces proteins, lipids, carbohydrate and
  nucleic acids biosynthesis
• Human FSH and FSHR was coexpressed using the
  baculovirus recombinant expression
• a and ß subunit sequences and the receptor
• Residues 1 to 111 represent the ß subunit
• Gly-Ser-rich linker of 15 residues
• Residues 1 to 92 represent the a subunit
• Residues 1 to 268 represent the extra cellular
  domain of FSHRB
• The intracellular domain is not expressed here

3
Glycoproteins have common a chain but they are
distinguished by ß chain
2 ß domains
2 a domains
FSH Receptor
4
The seat-belt position of ß on a forms the
specificity pocket.
a domain
ß domain
Specificity pocket
Seat-belt structure
ß seat-belt embraces a
5
2 basic residues from FSH, K91 and K51 bridge
with acidic residues D150 and D153
Lys 51
Asp 153
Lys 51
Lys 91
Lys 91
Asp 150
6
L55 and K179 of FSHR are inserted in a pocket in
FSH and L55 interacts with L99 and Y103 of FSH
beta and R42 of FSH alpha
Lys179
Leu99
Arg42
Tyr103
leu55
7
Receptor monomer
Beta sheets
Ile 2222
Arg 101
Glu 76
Lys 179
Leu 55
Leu 55, Lys 179, Ile 222 and the combination of
Glu 76 and Arg 101 confer specificity to the
receptor.
8
Conclusion This model can be used to other
glycoprotein hormone systems such as LH and TSH.

• Future research solve the structure of the
  unbound FSH. Evidence indicate that the structure
  of the free hormone might be different.
• Implication Infertility or Contraception

Than you Ramata Cisse BCMB 8010