A synthetic peptide encompassing two discontinuous regions of hFSH-beta subunit mimics the receptor binding surface of the hormone.
Synthetic peptides corresponding to discontinuous segments of the hFSH-beta subunit, amino acids 33-53 and 81-95, have been shown to interact with the follicle-stimulating hormone (FSH) receptor. In this study, we demonstrate that hFSH-beta-(33-53)-(81-95)-peptide amide, a synthetic peptide encompassing these binding regions, possesses higher affinity for the FSH receptor than either synthetic hFSH-beta-(33-53) or hFSH-beta-(81-95). This increased affinity suggests that each binding component is effectively interacting with the receptor, providing evidence that these two separate receptor binding regions of hFSH-beta form a continuous binding surface on the native molecule. These results also suggest that binding surfaces of very complex proteins, such as the heterodimeric glycoprotein hormone FSH, may be mimicked by a linear arrangement of its binding domains. A model based on energetics of the peptide-receptor interaction is also described. The results indicate that the affinity (Ka) of a peptide containing different binding domains can be approximated utilizing the product of the affinity constant of each binding domain (Ka = k1.k2...kn).
Santa-Coloma
T A
TA
Albany Medical College, Department of Biochemistry, NY 12208.
Crabb
J W
JW
Reichert
L E
LE
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D043373:Follicle Stimulating Hormone, Human; D037201:Follicle Stimulating Hormone, beta Subunit; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism*; D011869:Radioligand Assay; D011962:Receptors, FSH / Q000378:metabolism*; D013816:Thermodynamics
D043373:Follicle Stimulating Hormone, Human; D037201:Follicle Stimulating Hormone, beta Subunit; D010446:Peptide Fragments; D011962:Receptors, FSH; C072584:follicle stimulating hormone, beta subunit (33-53), human; C072585:follicle stimulating hormone, beta subunit (33-53)-(81-95)-peptide amide, human; C063489:follicle stimulating hormone, beta subunit (81-95), human; D005640:Follicle Stimulating Hormone