A. Naito and K. Nishimura Pages 135 - 145 ( 11 )
Determination of conformations and structures of opioid peptides in the membrane environments is an essential step to understand the action of the peptide to the specialized receptors. This information not only gains insight into the structure-function relationship of opioid peptide but also gives proper guidelines to design a new drug to have same neuroendocrine functions. This review provides the structural studies of three types of opioid peptide families such as enkephalin, β-endorphin and dynorphin in the solid states and the membrane environments. The structures of enkephalins show that they take β-bend, extended and double β-bend structures in the crystals. Moreover, enkephalin molecules take a variety of structures in the crystals and are easily converted to the other structures with slightly different torsion angles. On the other hand, β-bend structures are mostly seen in the membrane environments. Membrane bound structure of dynorphin shows that the N-terminus forms α-helixal structure and is inserted into the membrane with the helical axis almost perpendicular to the membrane surface. It is discussed that the helical region of the extracellular loop II of the κ- opioid receptor may interact with the helical region of dynorphin with a high affinity in the membrane environments. β- endorphin takes α-helical structure at N-terminus and the central regions and the rest of regions take unordered structure when they bind to the membrane. Since the membrane bound structures of opioid peptides differ from those of the solution states, membrane association is an important process for exerting the affinity and the selectivity to the specific opioid receptors.
Opioid peptide, Opioid receptor, Nuclear magnetic resonance, Membrane, Enkephalin, Dynorphin, Endorphin, Extracellular loop II
Yokohama National University,Graduate School of Engineering, 79-5 Tokiwadai, Hodogaya, Yokohama240-8501, Japan