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Hormone/growth factor PDB id
1fl7
Jmol
Contents
Protein chains
86 a.a. *
107 a.a. *
Ligands
NAG-NDG ×2
NAG-NAG-MAN
NAG-NAG ×2
NAG-NDG-MAN
SO4 ×2
* Residue conservation analysis
PDB id:
1fl7
Name: Hormone/growth factor
Title: Human follicle stimulating hormone
Structure: Follicle stimulating protein alpha chain. Chain: a, c. Synonym: glycoprotein hormones alpha chain. Engineered: yes. Follicle stimulating protein beta chain. Chain: b, d. Synonym: follitrophin beta chain. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: pituitary gland. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Other_details: homo sapiens, pituitary gland. Other_details: homo sapiens, pituitary gland
Biol. unit: Tetramer (from PQS)
Resolution:
3.00Å     R-factor:   0.259     R-free:   0.294
Authors: K.M.Fox,J.A.Dias,P.Van Roey
Key ref: K.M.Fox et al. (2001). Three-dimensional structure of human follicle-stimulating hormone. Mol Endocrinol, 15, 378-389. PubMed id: 11222739 DOI: 10.1210/me.15.3.378
Date:
11-Aug-00     Release date:   14-Mar-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01215  (GLHA_HUMAN) -  Glycoprotein hormones alpha chain
Seq:
Struc: 		116 a.a.
86 a.a.
Protein chains
Pfam   ArchSchema ?
P01225  (FSHB_HUMAN) -  Follitropin subunit beta
Seq:
Struc: 		129 a.a.
107 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     developmental growth   20 terms 
  Biochemical function     hormone activity     3 terms  

 

 
DOI no: 10.1210/me.15.3.378 Mol Endocrinol 15:378-389 (2001)
PubMed id: 11222739  
 
 
Three-dimensional structure of human follicle-stimulating hormone.
K.M.Fox, J.A.Dias, P.Van Roey.
 
  ABSTRACT  
 
The crystal structure of a betaThr26Ala mutant of human follicle-stimulating hormone (hFSH) has been determined to 3.0 A resolution. The hFSH mutant was expressed in baculovirus-infected Hi5 insect cells and purified by affinity chromatography, using a betahFSH-specific monoclonal antibody. The betaThr26Ala mutation results in elimination of the betaAsn24 glycosylation site, yielding protein more suitable for crystallization without affecting the receptor binding and signal transduction activity of the glycohormone. The crystal structure has two independent hFSH molecules in the asymmetric unit and a solvent content of about 80%. The alpha- and betasubunits of hFSH have similar folds, consisting of central cystine-knot motifs from which three beta-hairpins extend. The two subunits associate very tightly in a head-to-tail arrangement, forming an elongated, slightly curved structure, similar to that of human chorionic gonadotropin (hCG). The hFSH heterodimers differ only in the conformations of the amino and carboxy termini and the second loop of the beta-subunit (L2beta). Detailed comparison of the structures of hFSH and hCG reveals several differences in the beta-subunits that may be important with respect to receptor binding specificity or signal transduction. These differences include conformational changes and/or differential distributions of polar or charged residues in loops L3beta (hFSH residues 62-73), the cystine noose, or determinant loop (residues 87-94), and the carboxy-terminal loop (residues 94-104). An additional interesting feature of the hFSH structure is an extensive hydrophobic patch in the area formed by loops alphaL1, alphaL3, and betaL2. Glycosylation at alphaAsn52 is well known to be required for full signal transduction activity and heterodimer stability. The structure reveals an intersubunit hydrogen bonding interaction between this carbohydrate and betaTyr58, an indication of a mechanism by which the carbohydrate may stabilize the heterodimer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20800406 C.Liu, S.Dong, X.J.Xu, Y.Yin, Z.Shriver, I.Capila, J.Myette, and G.Venkataraman (2011).
Assessment of the quality and structural integrity of a complex glycoprotein mixture following extraction from the formulated biopharmaceutical drug product.
  J Pharm Biomed Anal, 54, 27-36.  
21044091 T.Müller, T.Hupfeld, J.Roessler, M.Simoni, J.Gromoll, and R.Behr (2011).
Molecular cloning and functional characterization of endogenous recombinant common marmoset monkey (Callithrix jacchus) follicle-stimulating hormone.
  J Med Primatol, 40, 111-119.  
20613903 Y.H.Park, S.J.Kim, B.H.Jeong, T.J.Herzog, J.Wright, J.Kitajewski, C.C.Rhim, P.R.Jang, J.B.Kang, and S.J.Kim (2010).
Follicular stimulating hormone enhances Notch 1 expression in SK-OV-3 ovarian cancer cells.
  J Gynecol Oncol, 21, 119-124.  
20067895 M.L.Kottler, N.Richard, O.Chabre, S.Alain, and J.Young (2009).
FSHbeta gene mutation in a female with delayed puberty and hypogonadism: response to recombinant human FSH.
  Folia Histochem Cytobiol, 47, S55-S58.  
19005656 H.W.Honegger, E.M.Dewey, and J.Ewer (2008).
Bursicon, the tanning hormone of insects: recent advances following the discovery of its molecular identity.
  J Comp Physiol A Neuroethol Sens Neural Behav Physiol, 194, 989.  
19267640 M.Freamat, and S.A.Sower (2008).
Glycoprotein hormone receptors in the sea lamprey Petromyzon marinus.
  Zoolog Sci, 25, 1037-1044.  
18084009 M.Ghadami, S.A.Salama, N.Khatoon, R.Chilvers, M.Nagamani, P.J.Chedrese, and A.Al-Hendy (2008).
Toward gene therapy of primary ovarian failure: adenovirus expressing human FSH receptor corrects the Finnish C566T mutation.
  Mol Hum Reprod, 14, 9.  
17059864 D.Puett, Y.Li, G.DeMars, K.Angelova, and F.Fanelli (2007).
A functional transmembrane complex: the luteinizing hormone receptor with bound ligand and G protein.
  Mol Cell Endocrinol, 260, 126-136.  
17358049 J.A.Wilken, and E.Bedows (2007).
A novel four-amino acid determinant defines conformational freedom within chorionic gonadotropin beta-subunits.
  Biochemistry, 46, 4417-4424.  
  17295898 K.Haller, A.Salumets, M.Grigorova, I.Talja, L.Salur, M.C.Béné, M.Laan, and R.Uibo (2007).
Putative predictors of antibodies against follicle-stimulating hormone in female infertility: a study based on in vitro fertilization patients.
  Am J Reprod Immunol, 57, 193-200.  
17227474 M.Grigorova, K.Rull, and M.Laan (2007).
Haplotype structure of FSHB, the beta-subunit gene for fertility-associated follicle-stimulating hormone: possible influence of balancing selection.
  Ann Hum Genet, 71, 18-28.  
18074397 P.Timmerman, W.C.Puijk, and R.H.Meloen (2007).
Functional reconstruction and synthetic mimicry of a conformational epitope using CLIPS technology.
  J Mol Recognit, 20, 283-299.  
17045735 Q.R.Fan, and W.A.Hendrickson (2007).
Assembly and structural characterization of an authentic complex between human follicle stimulating hormone and a hormone-binding ectodomain of its receptor.
  Mol Cell Endocrinol, 260, 73-82.  
17143726 S.R.Setlur, and R.R.Dighe (2007).
Single chain human chorionic gonadotropin, hCGalphabeta: effects of mutations in the alpha subunit on structure and bioactivity.
  Glycoconj J, 24, 97.  
17140726 T.F.Lerch, M.Xu, T.S.Jardetzky, K.E.Mayo, I.Radhakrishnan, R.Kazer, L.D.Shea, and T.K.Woodruff (2007).
The structures that underlie normal reproductive function.
  Mol Cell Endocrinol, 267, 1-5.  
17059863 W.Lin, M.P.Bernard, D.Cao, R.V.Myers, J.E.Kerrigan, and W.R.Moyle (2007).
Follitropin receptors contain cryptic ligand binding sites.
  Mol Cell Endocrinol, 260, 83-92.  
16467256 D.Puett, Y.Li, K.Angelova, G.Demars, T.P.Meehan, F.Fanelli, and P.Narayan (2005).
Structure-function relationships of the luteinizing hormone receptor.
  Ann N Y Acad Sci, 1061, 41-54.  
  16212648 K.Haller, C.Mathieu, K.Rull, K.Matt, M.C.Béné, and R.Uibo (2005).
IgG, IgA and IgM antibodies against FSH: serological markers of pathogenic autoimmunity or of normal immunoregulation?
  Am J Reprod Immunol, 54, 262-269.  
15812852 P.Timmerman, J.Beld, W.C.Puijk, and R.H.Meloen (2005).
Rapid and quantitative cyclization of multiple peptide loops onto synthetic scaffolds for structural mimicry of protein surfaces.
  Chembiochem, 6, 821-824.  
15662415 Q.R.Fan, and W.A.Hendrickson (2005).
Structure of human follicle-stimulating hormone in complex with its receptor.
  Nature, 433, 269-277.
PDB code: 1xwd
14585810 A.Jablonka-Shariff, and I.Boime (2004).
Luteinizing hormone and follicle-stimulating hormone exhibit different secretion patterns from cultured Madin-Darby canine kidney cells.
  Biol Reprod, 70, 649-655.  
15103132 A.McPherson, J.Day, and L.J.Harris (2004).
Crystals of the beta-subunit of bovine luteinizing hormone and indicators for the involvement of proteolysis in protein crystallization.
  Acta Crystallogr D Biol Crystallogr, 60, 872-877.  
15650352 R.Núñez Miguel, J.Sanders, J.Jeffreys, H.Depraetere, M.Evans, T.Richards, T.L.Blundell, B.Rees Smith, and J.Furmaniak (2004).
Analysis of the thyrotropin receptor-thyrotropin interaction by comparative modeling.
  Thyroid, 14, 991.  
15449706 W.Sebald, J.Nickel, J.L.Zhang, and T.D.Mueller (2004).
Molecular recognition in bone morphogenetic protein (BMP)/receptor interaction.
  Biol Chem, 385, 697-710.  
12700183 A.Ulloa-Aguirre, C.Timossi, J.Barrios-de-Tomasi, A.Maldonado, and P.Nayudu (2003).
Impact of carbohydrate heterogeneity in function of follicle-stimulating hormone: studies derived from in vitro and in vivo models.
  Biol Reprod, 69, 379-389.  
12773385 G.Smits, M.Campillo, C.Govaerts, V.Janssens, C.Richter, G.Vassart, L.Pardo, and S.Costagliola (2003).
Glycoprotein hormone receptors: determinants in leucine-rich repeats responsible for ligand specificity.
  EMBO J, 22, 2692-2703.  
  12045258 K.Nakabayashi, H.Matsumi, A.Bhalla, J.Bae, S.Mosselman, S.Y.Hsu, and A.J.Hsueh (2002).
Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor.
  J Clin Invest, 109, 1445-1452.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.