Structure and function of a minimal receptor activation domain of parathyroid hormone.
The structure and function of short-length amino terminal PTH analogues were studied. The substitution of Leu(7) with Phe in [Ala(3,10)Leu(7)Arg(11)]rPTH(1-11)NH(2) 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 [Ala(3,10)Leu(7)Arg(11)]rPTH(1-11)NH(2) caused nearly a complete loss of cAMP formation. Meanwhile, NMR analysis of [(Ala(1)/ Ser(1))Ala(3,10)(Leu(7)/Phe(7))Arg(11)]rPTH(1-11)NH(2) 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.
Lee
Eun Jin
EJ
Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. lsk@yumc.yonsei.ac.kr
Kim
Hai Young
HY
Cho
Min Kyu
MK
Lee
Weontae
W
Lim
Sung Kil
SK
D019943:Amino Acid Substitution; D000818:Animals; D002942:Circular Dichroism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D018374:LLC-PK1 Cells; D019906:Nuclear Magnetic Resonance, Biomolecular; D010281:Parathyroid Hormone / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics; D013329:Structure-Activity Relationship; D013552:Swine
D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1; D000242:Cyclic AMP