Structure and Function of a Minimal Receptor Activation Domain of Parathyroid Hormone.
10.3349/ymj.2004.45.3.419
- Author:
Eun Jin LEE
1
;
Hai Young KIM
;
Min Kyu CHO
;
Weontae LEE
;
Sung Kil LIM
Author Information
1. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea. lsk@yumc.yonsei.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Parathyroid hormone;
parathyroid hormone receptor;
cyclic AMP-generating activity;
nuclear magnetic resonance;
alpha-helix
- MeSH:
Amino Acid Substitution;
Animals;
Circular Dichroism;
Cyclic AMP/metabolism;
Human;
LLC-PK1 Cells;
Nuclear Magnetic Resonance, Biomolecular;
Parathyroid Hormone/*chemistry/*metabolism;
Protein Structure, Secondary;
Protein Structure, Tertiary;
Receptor, Parathyroid Hormone, Type 1/genetics;
Structure-Activity Relationship;
Support, Non-U.S. Gov't;
Swine
- From:Yonsei Medical Journal
2004;45(3):419-427
- CountryRepublic of Korea
- Language:English
-
Abstract:
The structure and function of short-length amino terminal PTH analogues were studied. The substitution of Leu7 with Phe in [Ala3, 10Leu7Arg11]rPTH (1-11) NH2 analogue peptides did not show any reduction in cAMP formation. Replacement of the 1st, 7th and 8th residues revealed different activities, depending upon the residue type. The substitution of Ala1 by Ser in [Ala3, 10Leu7Arg11]rPTH (1-11) NH2 caused nearly a complete loss of cAMP formation. Meanwhile, NMR analysis of [ (Ala1/ Ser1) Ala3, 10 (Leu7/Phe7) Arg11]rPTH (1-11) NH2 revealed an alpha- helical backbone structure with a flexible conformation at the carboxyl-terminus. The overall results suggest that 11-residue short oligopeptide analogues of PTH tend to form an alpha-helical structure and the different activities of those analogues could be associated with residue specificity rather than the secondary conformational structure.
