Conformation of Substance P in Neutral Phospholipid Micelles

A linear undecapeptide, Substance P (SP) is involved in a wide variety of physiological processes such as pain, inflammation, salivation, and hypertension. Tertiary structure of SP in dodecylphosphocholine (DPC) micelles has been investigated by CD, NMR spectroscopy, and DGII calculation. CD spectrum of SP in the presence of 7.5 mM DPC micelles does not show any favorable secondary structure. The tertiary structure determined by NMR spectroscopy and DGII calculation shows that the Phe7-Phr8-Gly9-Leu10 region adopts a turn structure, while the N-terminal region is quite flexible. Both prolines in SP exist preferentially as the trans isoforms and the aromatic ring of Phe7 protrudes outward. Conformation of SP may be restrained by the contact of the Phe7 aromatic ring with the hydrophobic side chains of the DPC micelles and this interaction induces a turn structure. Structure of SP in aqueous solution in the presence of DPC micelles can represent a good model to study the conformation recognized by the receptor near neutral membrane.