Document Detail

NMR study of the conformation and localization of porcine galanin in SDS micelles. Comparison with an inactive analog and a galanin receptor antagonist.
MedLine Citation:
PMID:  9636064     Owner:  NLM     Status:  MEDLINE    
Galanin is a 29/30-residue neuro-endocrine peptide which performs its many important physiological functions via a membrane-bound receptor. By using two-dimensional proton NMR spectroscopy, complete relaxation matrix analysis, and simulated annealing, the conformation of porcine galanin was determined in a membrane-mimicking solvent containing sodium dodecyl sulfate (SDS) micelles. The final family of calculated structures displays three well-defined beta- or gamma-turn regions, comprising residues 1-5, 7-10, and 24-27, but has otherwise a random conformation. The receptor-interacting N-terminal part, residues 1-5, was found to be best defined with a backbone RMSD value of 0.12 A. The mode of association between galanin and the SDS micelle was determined by observing the broadening effect on proton resonances, when spin-labeled 5- and 12-doxyl stearate molecules were added. It was concluded that galanin is located close to the surface of the micelle with two regions, residues 6-9 and 24-29, as well as two single residues, 18 and 21, reaching out into the aqueous solvent. Additional NMR studies were carried out on an inactive analogue, Ala2-galanin, and an antagonist M40. The results show that the proton resonances of galanin and M40 have identical chemical shifts in the N-terminal receptor-interacting region, indicating similar solution structures in this region. For Ala2-galanin, the same region displays a spectral heterogeneity with chemical shifts clearly different from the other two peptides, indicative of different secondary structures. These results may provide a structural background for the antagonist activity of M40 and the hormonal inactivity of Ala2-galanin, as compared to galanin.
A Ohman; P O Lycksell; A Juréus; U Langel; T Bartfai; A Gräslund
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemistry     Volume:  37     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-07-20     Completed Date:  1998-07-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  9169-78     Citation Subset:  IM    
Department of Biophysics, Stockholm University, Sweden.
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MeSH Terms
Alanine / chemistry
Amino Acid Sequence
Galanin / analogs & derivatives,  chemistry*,  metabolism*
Molecular Sequence Data
Nuclear Magnetic Resonance, Biomolecular
Peptide Fragments / chemistry*
Protein Conformation*
Receptors, Galanin
Receptors, Neuropeptide / antagonists & inhibitors,  chemistry*
Sodium Dodecyl Sulfate*
Spin Labels
Reg. No./Substance:
0/Amides; 0/M40; 0/Micelles; 0/Peptide Fragments; 0/Protons; 0/Receptors, Galanin; 0/Receptors, Neuropeptide; 0/Spin Labels; 151-21-3/Sodium Dodecyl Sulfate; 56-41-7/Alanine; 88813-36-9/Galanin

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