STUDY OF HUMAN CALCITONIN FIBRILLATION BY PROTON NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

被引:40
作者
KANAORI, K [1 ]
NOSAKA, AY [1 ]
机构
[1] CIBA GEIGY JAPAN LTD, INT RES LABS, TAKARAZUKA, HYOGO 665, JAPAN
关键词
D O I
10.1021/bi00038a006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The fibrillation of human calcitonin (hCT) has been investigated by NMR in aqueous solution. The time course of proton one- and two-dimensional NMR spectra of hCT (80 mg/mL at pH 2.9) was measured during the fibrillation. It showed a gradual broadening of the peptide peaks, followed by a rapid broadening and subsequent disappearance of the peaks. The gradual broadening can be attributed to equilibrium between monomer and associated hCT, whereas the rapid broadening can be attributed to formation of aggregates and to gelation of the peptide solution. All the peptide peaks did not broaden and disappear simultaneously. Peaks of residues in the N-terminal (Cys(1)-Cys(7)) and central (Met(8)-Pro(23)) regions broadened and disappeared faster during the gradual broadening than those in the C-terminal region (Gln(24)-Pro(32)). Moreover, in the N-terminal and central residues, peaks of Cys(1), Leu(4,9), Met(8), Tyr(12), Asp(15), and Phe(16,19,22) disappeared faster than those of Asn(3,17), Ser(5), Cys(7), Gln(14), Lys(18), and His(20) Hydrogen-deuterium exchange of amide protons indicated the formation of hydrogen bonds caused by association of hCT molecules. The amphiphilicity of the peptide appears to be important for the hCT association.
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页码:12138 / 12143
页数:6
相关论文
共 30 条
[1]  
ARVINTE T, 1993, J BIOL CHEM, V268, P6415
[2]  
ARVINTE T, 1992, Patent No. 0490549
[3]   CALCITONIN - PHYSIOLOGY AND PATHO-PHYSIOLOGY [J].
AUSTIN, LA ;
HEATH, H .
NEW ENGLAND JOURNAL OF MEDICINE, 1981, 304 (05) :269-278
[4]   PRACTICAL ASPECTS OF TWO-DIMENSIONAL TRANSVERSE NOE SPECTROSCOPY [J].
BAX, A ;
DAVIS, DG .
JOURNAL OF MAGNETIC RESONANCE, 1985, 63 (01) :207-213
[5]   SEQUENTIAL RESONANCE ASSIGNMENTS IN PROTEIN H-1 NUCLEAR MAGNETIC-RESONANCE SPECTRA - COMPUTATION OF STERICALLY ALLOWED PROTON PROTON DISTANCES AND STATISTICAL-ANALYSIS OF PROTON PROTON DISTANCES IN SINGLE-CRYSTAL PROTEIN CONFORMATIONS [J].
BILLETER, M ;
BRAUN, W ;
WUTHRICH, K .
JOURNAL OF MOLECULAR BIOLOGY, 1982, 155 (03) :321-346
[6]   COHERENCE TRANSFER BY ISOTROPIC MIXING - APPLICATION TO PROTON CORRELATION SPECTROSCOPY [J].
BRAUNSCHWEILER, L ;
ERNST, RR .
JOURNAL OF MAGNETIC RESONANCE, 1983, 53 (03) :521-528
[7]   EVIDENCE FOR CALCITONIN - A NEW HORMONE FROM PARATHYROID THAT LOWERS BLOOD CALCIUM [J].
COPP, DH ;
DAVIDSON, AG ;
HENZE, KG ;
CHENEY, BA ;
CAMERON, EC .
ENDOCRINOLOGY, 1962, 70 (05) :638-+
[8]   ASSIGNMENT OF COMPLEX H-1-NMR SPECTRA VIA TWO-DIMENSIONAL HOMONUCLEAR HARTMANN-HAHN SPECTROSCOPY [J].
DAVIS, DG ;
BAX, A .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (09) :2820-2821
[9]  
Doi M., 1990, PEPTIDES CHEM STRUCT, P165
[10]   KINETICS OF SICKLE HEMOGLOBIN POLYMERIZATION .2. A DOUBLE NUCLEATION MECHANISM [J].
FERRONE, FA ;
HOFRICHTER, J ;
EATON, WA .
JOURNAL OF MOLECULAR BIOLOGY, 1985, 183 (04) :611-631