NMR study of the solution conformation of rat atrial natriuretic factor 7-23 in sodium dodecyl sulfate micelles.
The conformation of the cyclic portion (7-23) of naturally occurring rat atrial natriuretic factor, ANF(1-28), has been examined in sodium dodecyl sulfate (SDS) micelles using high-resolution NMR techniques. Evidence is presented which shows that ANF(7-23) has several regions of definable structure in SDS micelles which were not observed in earlier studies in bulk solvents. The 1H NMR resonances of ANF(7-23) in SDS micelles were assigned using sequential assignment techniques, and the conformational properties were analyzed primarily from proton-proton distances obtained from the quantitative analysis of two-dimensional nuclear Overhauser effect spectra. Three-dimensional structures consistent with the NMR data were generated by using distance geometry and constrained minimization/dynamics. Several similar but not identical structures were found which adequately satisfied the NMR constraints. Although none of the structures adopted a standard secondary structure, the conformations of three different sections of the peptide, 8-13, 14-17, and 18-21, were nearly identical in all of the predicted structures when individually superimposed.
Olejniczak
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Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064.
Gampe
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RT
Rockway
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Fesik
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SW
D000818:Animals; D009320:Atrial Natriuretic Factor; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D010446:Peptide Fragments; D011487:Protein Conformation; D051381:Rats; D012967:Sodium Dodecyl Sulfate; D012996:Solutions
D008823:Micelles; D010446:Peptide Fragments; D012996:Solutions; C472610:atrial natriuretic peptide, rat; D012967:Sodium Dodecyl Sulfate; D009320:Atrial Natriuretic Factor; C057820:atrial natriuretic factor (7-23)