Does the solid-state structure of endothelin-1 provide insights concerning the solution-state conformational...

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biophysics

Background:

• Endothelin-1 (ET-1) is a potent vasoconstrictor with a complex structure.
• Previous studies proposed different structural models for ET-1 in solid-state versus solution.
• Understanding ET-1's solution conformation is crucial for its biological activity.

Purpose of the Study:

• To present additional Nuclear Magnetic Resonance (NMR) data for endothelin-1.
• To support the existence of a helical structure in solution.
• To compare solution structure with existing solid-state models.

Main Methods:

• Analysis of Nuclear Overhauser Effect (NOE) ratios and chemical shifts from NMR spectroscopy.
• Investigated ET-1 in aqueous media with polar organic co-solvents (acetonitrile, acetic acid, ethylene glycol).
• Compared NMR data with reported X-ray crystallography and solids-state structures.

Main Results:

• NMR data support a helical structure in endothelin-1, initiated at Lys9 and extending to Cys15.
• This solution helical structure is not predicted by the reported solids-state X-ray structure.
• The helical preference remains consistent across different polar organic co-solvents.

Conclusions:

• The helical structure observed in endothelin-1 crystals is likely influenced by intermolecular interactions.
• This crystal structure does not represent the significant conformational equilibrium of monomeric ET-1 in solution.
• NMR data provide a more accurate representation of endothelin-1's biologically relevant solution conformation.