Antigenic structure of bovine growth hormone: location of a growth enhancing region.
Site-directed antisera generated by peptide immunization have been used to study the antigenicity of bovine growth hormone (bGH). Prediction of sequential antigenic sites has been performed using secondary structure information derived from the 'Protean' prediction routine. The structures predicted by this programme agree closely with the corresponding structure of GH recently derived from crystallographic studies. We have previously shown that the binding of monoclonal antibodies of particular epitope specificity to human or bovine GH results in significant enhancement of hormonal activity in vivo; however, the sites recognized by these antibodies were not known. Here we identify a sequence region, corresponding to a loop structure joining helices 3 and 4, which, is associated with the growth enhancement phenomenon. Antisera raised to either of two overlapping peptides (residues 120-140 and 134-154) significantly increase the biological activity of GH in vivo. Antisera directed to other regions on the GH molecule failed to demonstrate this property. Coincidentally, the sites recognized by the growth-enhancing anti-peptide antisera overlap with the site on GH which is highly susceptible to proteolytic cleavage; such cleavage has been shown in some cases to result in hormone enhancement.
Aston
R
R
Molecular Biology Laboratory, CSIRO Division of Biotechnology, Sydney, Australia.
Rathjen
D A
DA
Holder
A T
AT
Bender
V
V
Trigg
T E
TE
Cowan
K
K
Edwards
J A
JA
Cowden
W B
WB
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens; D001667:Binding, Competitive; D002417:Cattle; D000939:Epitopes; D006128:Growth / Q000187:drug effects; D013006:Growth Hormone / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D011487:Protein Conformation; D011869:Radioligand Assay; D012756:Sheep; D013329:Structure-Activity Relationship; D013552:Swine
D000911:Antibodies, Monoclonal; D000941:Antigens; D000939:Epitopes; D010455:Peptides; D013006:Growth Hormone