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Structure of human parathyroid hormone 1-37 in solution
U C Marx1, S Austermann, P Bayer
1Lehrstuhl für Biochemie, Universität Bayreuth, Federal Republic of Germany.
The Journal of Biological Chemistry
|June 23, 1995
Summary
Human parathyroid hormone (hPTH) (1-37) adopts a helical structure with hydrophobic interactions, revealing its tertiary structure. The N-terminal region is flexible, while distinct helical and turn regions are stabilized by specific amino acid interactions.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Endocrinology
Background:
- Human parathyroid hormone (hPTH) (1-37) is biologically active, influencing serum calcium concentration and inducing DNA synthesis.
- The signal pathway for hPTH-induced DNA synthesis remains largely unknown.
- Understanding the structure of hPTH (1-37) is crucial for elucidating its biological functions.
Purpose of the Study:
- To investigate the three-dimensional structure of human parathyroid hormone (hPTH) (1-37) in aqueous solution under physiological conditions.
- To identify structural elements and interactions that contribute to the biological activity of hPTH (1-37).
Main Methods:
- Circular dichroism (CD) spectroscopy.
- Ultracentrifugation.
- Nuclear magnetic resonance (NMR) spectroscopy, including 2D NMR techniques (DQF-COSY, NOESY, TOCSY).
- Molecular dynamics (MD) calculations.
Main Results:
- hPTH (1-37) adopts a predominantly helical structure in solution, stabilized by hydrophobic interactions that define its tertiary structure.
- A stable alpha-helical region exists between Ile5 and Asn10, followed by a flexible linker (Gly12, Lys13) and a defined turn region (His14-Ser17).
- A second alpha-helix spans from Ser17 to at least Leu28, with hydrophobic interactions (e.g., Trp23-Leu15) stabilizing the structure, which remained stable over 200 ps MD simulations.
Conclusions:
- The N-terminal four amino acids of hPTH (1-37) exhibit conformational flexibility.
- Specific helical and turn regions, stabilized by hydrophobic interactions, are key structural features of hPTH (1-37).
- The determined structure provides insights into the molecular mechanisms underlying hPTH's biological activity, particularly its role in calcium regulation.