Solution conformation of salmon calcitonin in sodium dodecyl sulfate micelles as determined by two-dimensional NMR and distance geometry calculations

The 32 amino acid hormone salmon calcitonin was studied at pH 3.7 and 7.4 by two-dimensional NMR in sodium dodecyl sulfate (SDS) micelles at 310 K. The spectrum was fully assigned, and the secondary structure was obtained from nuclear Overhauser enhancement spectroscopy (NOESY), 3JHN alpha coupling...

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Bibliographic Details
Published in:Biochemistry (Easton) 1991-10, Vol.30 (43), p.10444-10450
Main Authors: Motta, Andrea, Pastore, Annalisa, Goud, Nagana A, Castiglione Morelli, Maria A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Aminoacids, peptides. Hormones. Neuropeptides
Analytical, structural and metabolic biochemistry
Animals
Biological and medical sciences
calcitonin
Calcitonin - chemistry
Calcitonin - genetics
Fundamental and applied biological sciences. Psychology
Magnetic Resonance Spectroscopy
Marine
Micelles
Molecular Sequence Data
molecular structure
nuclear magnetic resonance
pH effects
Protein Conformation
Proteins
Salmon
Salmonidae
sodium dodecyl sulfate
Sodium Dodecyl Sulfate - chemistry
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Summary:The 32 amino acid hormone salmon calcitonin was studied at pH 3.7 and 7.4 by two-dimensional NMR in sodium dodecyl sulfate (SDS) micelles at 310 K. The spectrum was fully assigned, and the secondary structure was obtained from nuclear Overhauser enhancement spectroscopy (NOESY), 3JHN alpha coupling constants, and slowly exchanging amide data. Three-dimensional structures consistent with NMR data were generated by using distance geometry calculations. A set of 260 interproton distances, derived from NOESY, and hydrogen-bond constraints, obtained from analysis of the amide exchange, were used. From the initial random conformations, 13 distance geometry structures with minimal violations were selected for further refinement with restrained energy minimization. In SDS, at both pHs, the main conformational feature of the hormone is an alpha-helix from Thr6 through Tyr22, thus including the amphipathic 8-22 segment and two residues of the Cys1-Cys7 N-terminal loop. The C-terminal decapeptide forms a loop folded back toward the helix. The biological significance of this conformation is discussed.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00107a012