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Structure-function studies on human growth hormone. Evidence that tertiary structure is essential for biological
International Journal of Peptide and Protein Research
|July 1, 1986
Summary
The conformation of human growth hormone (hGH) is crucial for its biological and ligand binding activity. Modified hGH with retained native conformation showed high potency and binding affinity, indicating a 3D structure for its active sites.
Area of Science:
- Endocrinology
- Protein Chemistry
- Molecular Biology
Background:
- Human pituitary growth hormone (hGH) is a key endocrine protein with significant biological and ligand-binding functions.
- Understanding the structure-activity relationship of hGH is vital for developing effective therapeutic strategies.
- Previous studies established in vivo and in vitro assays for hGH activity and binding.
Purpose of the Study:
- To investigate the relationship between the conformation of human growth hormone (hGH) and its biological activity, including somatotropic and lactogenic functions.
- To compare conformational properties with ligand binding affinities in various hGH derivatives.
- To determine the structural basis for hGH's biological potency and receptor interactions.
Main Methods:
- Comparative analysis of published conformational data (circular dichroism, tryptic digestion) for native hGH and its derivatives.
- In vivo assays: rat tibia test (somatotropic) and pigeon crop-sac assay (lactogenic).
- In vitro assays: radioimmunoassays (RIAs) with various anti-hGH and anti-hCS sera, and radioreceptor assays using rabbit liver (somatotropic) and mammary (lactogenic) membranes.
Main Results:
- Unfragmented, chemically modified hGH derivatives showed a strong correlation between retained native conformation and preserved in vivo potency and in vitro binding affinities.
- hGH fragments lacked activity in all tested radioimmunoassays and radioreceptor assays.
- hGH derivatives with polypeptide backbone gaps (6 or 12 residues) exhibited full or enhanced potency, retained RIA activity, and showed high activity in radioreceptor assays, with one derivative (missing residues 135-140) preserving native conformation.
Conclusions:
- Retention of native conformation and conformational stability in modified hGH is directly linked to maintaining high in vivo biological potency and in vitro binding affinity.
- The biologically active, receptor-binding, and immunoreactive sites of hGH are intrinsically three-dimensional.
- Structural integrity is paramount for the multifaceted functions of human growth hormone.