Crystal structure of human chorionic gonadotropin

@article{Lapthorn1994CrystalSO,
  title={Crystal structure of human chorionic gonadotropin},
  author={Adrian J. Lapthorn and Daniel Charles Harris and Allison Littlejohn and Joyce W. Lustbader and Robert E. Canfield and K. J. Machin and Francis J. Morgan and Neil W. Isaacs},
  journal={Nature},
  year={1994},
  volume={369},
  pages={455-461}
}
The three-dimensional structure of human chorionic gonadotropin shows that each of its two different subunits has a similar topology, with three disulphide bonds forming a cystine knot. This same folding motif is found in some protein growth factors. The heterodimer is stabilized by a segment of the β-subunit which wraps around the α-subunit and is covalently linked like a seat belt by the disulphide Cys 26–Cys 110. This extraordinary feature appears to be essential not only for the association… 
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The b-GlcNAc(78) is tightly associated with the hydrophobic protein-core in between the b-hairpins and is shielded from the solvent, based on the NOEs from the axial H1, H3, H5 atoms and the N-acetyl protons of b- GlcNA c to theprotein-core.
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References

SHOWING 1-10 OF 46 REFERENCES
Crystal structure of human platelet‐derived growth factor BB.
TLDR
The crystal structure of the homodimeric BB isoform of human recombinant platelet-derived growth factor (PDGF-BB) has been determined by X-ray analysis to 3.0 A resolution and it is shown that dimerization leads to the clustering of three surface loops at each end of the elongated dimer, which most probably form the receptor recognition sites.
Structure and Function of the Gonadotropin Free α Molecule of Pregnancy
TLDR
The α polypeptide may combine noncovalently with any of several β-subunits to form one of the heterodimeric hormones, LH, FSH, TSH or hCG.
Structure of the human chorionic gonadotropin beta-subunit fragment from pregnancy urine.
A major portion of the hCG immunoreactivity detectable in pregnancy urine is derived from a fragment of hCG beta. This lacks the COOH-terminal portion of hCG beta, but retains immunoreactivity with
Crystallization and characterization of human chorionic gonadotropin in chemically deglycosylated and enzymatically desialylated states.
TLDR
It is suggested that the high and heterogeneous carbohydrate content of the glycoprotein hormones inhibited their crystallization, and it is the negatively charged surface sugars and neither the total carbohydrate content nor its heterogeneity which interferes with crystal formation.
A region in the human glycoprotein hormone alpha-subunit important in holoprotein formation and receptor binding.
TLDR
Using site-directed mutagenesis of the human glycoprotein hormone alpha-subunit, it is shown that single replacements of Ala36 and Pro38 with Glu and Asp result in mutant subunits that do not bind significantly to hCG beta.
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